Academic literature on the topic 'KIR3DL1'
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Journal articles on the topic "KIR3DL1"
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Harvey, D., J. J. Pointon, C. Sleator, A. Meenagh, C. Farrar, J. Y. Sun, D. Senitzer, D. Middleton, M. A. Brown, and B. P. Wordsworth. "Analysis of killer immunoglobulin-like receptor genes in ankylosing spondylitis." Annals of the Rheumatic Diseases 68, no. 4 (November 19, 2008): 595–98. http://dx.doi.org/10.1136/ard.2008.095927.
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Objectives:To assess the possible association of killer immunoglobulin-like receptor (KIR) genes, specifically KIR3DL1, KIR3DS1 and KIR3DL2, with ankylosing spondylitis (AS).Methods:14 KIR genes were genotyped in 200 UK patients with AS and 405 healthy controls using multiplex polymerase chain reaction. Sequence-specific oligonucleotide probes were used to subtype 368 cases with AS and 366 controls for 12 KIR3DL2 alleles. Differences in KIR genotypes and KIR3DL2 allele frequencies were assessed using the χ2 test.Results:KIR3DL1 and KIR3DS1 gene frequencies were very similar in cases with AS and controls (odds ratio = 1.5, 95% confidence interval 0.8 to 3.0, and odds ratio = 1.02, 95% confidence interval 0.2 to 5.3, respectively). KIR3DL2 allele frequencies were not significantly different between cases with AS and controls.Conclusions:Neither the KIR gene content of particular KIR haplotypes nor KIR3DL2 polymorphisms contribute to AS.
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Forlenza, Christopher J., Jeanette E. Boudreau, Junting Zheng, Jean-Benoît Le Luduec, Elizabeth Chamberlain, Glenn Heller, Nai-Kong V. Cheung, and Katharine C. Hsu. "KIR3DL1 Allelic Polymorphism and HLA-B Epitopes Modulate Response to Anti-GD2 Monoclonal Antibody in Patients With Neuroblastoma." Journal of Clinical Oncology 34, no. 21 (July 20, 2016): 2443–51. http://dx.doi.org/10.1200/jco.2015.64.9558.
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Purpose In patients with neuroblastoma (NB), treatment with anti-GD2 monoclonal antibody (mAb) directs natural killer (NK) cell–mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cells. However, tumor cytotoxicity is attenuated by ligation of inhibitory killer immunoglobulin-like receptors (KIRs) by HLA class I molecules. KIR3DL1 polymorphism influences its ability to engage HLA-Bw4 ligands. We tested the hypothesis that poorly interacting combinations of KIR3DL1 and HLA ligands are more permissive of mAb-mediated antitumor effect. Methods KIR3DL1 and HLA-B subtyping were performed with a multiplex intermediate-resolution polymerase chain reaction assay for a cohort of 245 patients who were treated with antibody 3F8 for high-risk NB. Patient outcomes were analyzed according to expected degree of interaction between KIR3DL1 and HLA-B subtypes and grouped as strong, weak, or noninteractors. A comparison of NK response to 3F8 mAb opsonized NB cells between strong- and noninteracting donors was performed by flow cytometry. Results KIR3DL1 and HLA-B subtype combinations associated with noninteraction as a result of lack of receptor expression [KIR3DL1(−)], failure of interaction with inhibitory ligands [KIR3DS1(+)], or absence of KIR ligands resulted in significantly improved overall and progression-free survival. Patients with KIR3DL1 and HLA-B subtype combinations that were predictive of weak interaction had superior outcomes compared with those that were predictive of strong interaction; however, both groups were inferior to those with noninteracting subtype combinations. In vitro analysis of 3F8-mediated ADCC showed that KIR3DL1(−) and 3DS1(+) NK cells were insensitive to inhibition by HLA-Bw4–expressing NB targets. Conclusion We conclude that KIR3LD1 and HLA-B allele combinations can have a prognostic impact on patient survival after treatment with anti-GD2 mAb that relies on NK-ADCC. The survival advantage seen in noninteracting combinations supports the therapeutic disinhibition of individuals with strongly interacting KIR and ligand pairs.
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Vojvodic, Svetlana, and D. Ademovic-Sazdanic. "Killer-cell immunoglobulin-like receptor genes linkage disequilibrium analysis in population of Vojvodina." Genetika 47, no. 2 (2015): 439–50. http://dx.doi.org/10.2298/gensr1502439v.
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Killer Immunoglobulin-like Receptors (KIRs) form a group of regulatory molecules that modulate cytolytic activity of natural killer cells and T cells through interaction with specific human leukocyte antigen (HLA) molecules on target cells. KIRs are encoded by the family of 16 homologous genes that vary substantially between haplotypes and display sequence polymorphism with allelic variation that also contributes to diversity within the complex. The aim of the study is to estimate two locus linkage disequilibrium for 16 KIR loci. In this study, we report the evaluation of KIR gene content, allele, haplotype and genotype frequencies in 175 unrelated healthy individuals from Vojvodina who were KIR typed by polymerase chain reaction-sequence specific primers genotyping assay. The linkage disequilibrium (LD) was studied at the structural level (presence or absence of 16 KIR genes). Our results revealed that linkage disequilibrium is present between telomeric gene pairs KIR2DL1~KIR2DL4, KIR2DP1~KIR2DL4, KIR2DP1~KIR3DL1, KIR2DL1~KIR3DL2, KIR2DP1~KIR3DL2, KIR2DL4~KIR3DL1, KIR2DL4~KIR2DS4, KIR2DL4~KIR3DL2 where (r2=1), but positive association between KIR genes, with higher observed than expected haplotype frequencies were observed for KIR3DS1~KIR2DS1 and KIR2DL5~KIR2DS1 pair of genes (r2=0.646) and (r2=0.371), respectively. Thirty-eight different genotypes were identified, where 12% of the individuals have unique genotype, present in only one person. Our results will help to understand the genetic background of the Vojvodina population, in illustrating the population migration events in the northern part of Serbia, in explaining the extensive genetic admixture amongst the different ethnic groups of the region and also in KIR-related disease studies.
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O'Connor, Geraldine M., Julian P. Vivian, Emma Gostick, Phillip Pymm, Bernard A. P. Lafont, David A. Price, Jamie Rossjohn, Andrew G. Brooks, and Daniel W. McVicar. "Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1." Journal of Virology 89, no. 10 (March 4, 2015): 5213–21. http://dx.doi.org/10.1128/jvi.03586-14.
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ABSTRACTKiller cell immunoglobulin-like receptors (KIRs) play an important role in the activation of natural killer (NK) cells, which in turn contribute to the effective immune control of many viral infections. In the context of HIV infection, the closely related KIR3DL1 and KIR3DS1 molecules, in particular, have been associated with disease outcome. Inhibitory signals via KIR3DL1 are disrupted by downregulation of HLA class I ligands on the infected cell surface and can also be impacted by changes in the presented peptide repertoire. In contrast, the activatory ligands for KIR3DS1 remain obscure. We used a structure-driven approach to define the characteristics of HLA class I-restricted peptides that interact with KIR3DL1 and KIR3DS1. In the case of HLA-B*57:01, we used this knowledge to identify bona fide HIV-derived peptide epitopes with similar properties. Two such peptides facilitated productive interactions between HLA-B*57:01 and KIR3DS1. These data reveal the presence of KIR3DS1 ligands within the HIV-specific peptide repertoire presented by a protective HLA class I allotype, thereby enhancing our mechanistic understanding of the processes that enable NK cells to impact disease outcome.IMPORTANCENatural killer (NK) cells are implicated as determinants of immune control in many viral infections, but the precise molecular mechanisms that initiate and control these responses are unclear. The activating receptor KIR3DS1 in combination with HLA-Bw4 has been associated with better outcomes in HIV infection. However, evidence of a direct interaction between these molecules is lacking. In this study, we demonstrate that KIR3DS1 recognition of HLA-Bw4 is peptide dependent. We also identify HIV-derived peptide epitopes presented by the protective HLA-B*57:01 allotype that facilitate productive interactions with KIR3DS1. Collectively, these findings suggest a mechanism whereby changes in the peptide repertoire associated with viral infection provide a trigger for KIR3DS1 engagement and NK cell activation.
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Erer, B., M. Takeuchi, D. Ustek, I. Tugal-Tutkun, E. Seyahi, Y. Özyazgan, J. Duymaz-Tozkir, et al. "Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behçet’s disease." Genes & Immunity 17, no. 7 (October 6, 2016): 396–99. http://dx.doi.org/10.1038/gene.2016.36.
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Gabriel, Ian H., Ruhena Sergeant, Richard Szydlo, Jane F. Apperley, Hugues deLavallade, Abdullah Alsuliman, Ahmad Khoder, et al. "Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma." Blood 116, no. 12 (September 23, 2010): 2033–39. http://dx.doi.org/10.1182/blood-2010-03-273706.
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Abstract Natural killer (NK) cells exert antimyeloma cytotoxicity. The balance between inhibition and activation of NK-cells played by the inherited repertoire of killer immunoglobulin-like receptor (KIR) genes therefore may influence prognosis. One hundred eighty-two patients with multiple myeloma (MM) were analyzed for KIR repertoire. Multivariate analysis showed that progression-free survival (PFS) after autologous stem cell transplantation (ASCT) was significantly shorter for patients who are KIR3DS1+ (P = .01). This was most evident for patients in complete or partial remission (good risk; GR) at ASCT. The relative risk (RR) of progression or death for patients with KIR3DS1+ compared with KIR3DS1− was 1.9 (95% CI, 1.3-3.1; P = .002). The most significant difference in PFS was observed in patients with GR KIR3DS1+ in whom HLA-Bw4, the ligand for the corresponding inhibitory receptor KIR3DL1, was missing. Patients with KIR3DS1+KIR3DL1+HLA-Bw4− had a significantly shorter PFS than patients who were KIR3DS1−, translating to a difference in median PFS of 12 months (12.2 vs 24 months; P = .002). Our data show that KIR–human leukocyte antigen immunogenetics represent a novel prognostic tool for patients with myeloma, shown here in the context of ASCT, and that KIR3DS1 positivity may identify patients at greater risk of progression.
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Jia, Jie, Keqin Lin, Hao Sun, Jie‐Jie Dai, and Zhao‐Qing Yang. "Identification of two novel KIR3DL1 subtypes, KIR3DL1*0010104 and KIR3DL1*0010105." HLA 93, no. 2-3 (January 16, 2019): 138–39. http://dx.doi.org/10.1111/tan.13457.
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Gabriel, Ian H., Ruhena Sargent, Hugues de Lavallade, Richard Szydlo, Jane Apperley, Ahmad Khoder, Abdullah Alsuliman, et al. "Presence of the Killer Immunoglobulin-Like Gene KIR3DS1 Is Associated with Poor Progression Free and Overall Survival Following Autologous Stem Cell Transplantation in Patients with Myeloma." Blood 114, no. 22 (November 20, 2009): 2840. http://dx.doi.org/10.1182/blood.v114.22.2840.2840.
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Abstract Abstract 2840 Poster Board II-816 Multiple myeloma (MM) remains incurable with a median survival of 3–4 years. Despite high dose therapy and autologous stem cell transplant (ASCT) most patients relapse with median progression-free survival (PFS) of 2.5–4 years and overall survival (OS) of 4–5 years. Although allogeneic SCT (allo-SCT) is potentially curative due to a graft-versus-myeloma effect, its applicability is significantly limited by high transplant related mortality (TRM). Therefore, the identification of additional independent biological predictors of outcome is required in order to tailor therapy to disease. Natural killer (NK) cells provide first line defence against tumors. NK cells have been shown to recognize and kill myeloma cells both in the allogeneic and autologous settings and donor NK genotype has been shown to influence leukemia free survival following allo-SCT. The aim of this study was to investigate the impact of KIR genotype on event-free (EFS) and OS following ASCT for MM. We performed KIR genotyping on 190 patients with MM receiving a first autologous transplant. KIR genotype and haplotype frequencies were comparable to those published for normal controls. Factors found on univariate analysis to be associated with a shorter EFS included haplotype Bx (containing at least 1 of the KIR B haplotype-defining loci- KIR2DL5, 2DS1, 2DS2, 2DS3, 2DS5, or 3DS1) (median 547 vs 656 days, P = 0.036), ≥3 activating KIR genes (median 547 vs 615 days, P = 0.046), the presence of activating KIR genes KIR2DS1 and KIR3DS1 (median 456 vs 589 days, and 464 vs 619 days, P=0.045 and 0.01 respectively). Disease status at ASCT was the most highly predictive factor for EFS. In patients with good risk disease (CR or PR at ASCT) KIR3DS1 status was highly predictive for EFS 464 days (341–586) vs 731 days (599–862) (P = 0.003) and OS 807days (713-901) vs 967 (925-1009) (P=0.023). KIR3DS1 was not predictive in patients with poor risk disease (P=0.36). Of note KIR3DS1+ve patients were equally represented in good risk (CR and PR) and poor risk (refractory or relapsed) groups at ASCT (around 30% in both groups). Notably the median EFS for KIR3DS1+ good risk patients was not significantly different to poor risk disease patients (P = 0.061). ASCT outcome was then determined according to 3 main groups based on disease status and KIR3DS1 status; A: Good Risk, KIR3DS1-ve; B: Good Risk, KIRDS1+ ve; and C Poor risk (KIR3DS1+ve or -ve). The RR of relapse or death was 1.0, 1.9 (P=0.002, 95% CI 1.3-3.1), and 3.0 (P=0.0001, 95% CI 1.9-4.8) respectively. By multivariate analysis, after adjusting for the presence of adverse cytogenetics and serum albumin and β2m, the KIR3DS1 status and grouping remained highly predictive of poor EFS, RR of 1.0, 2.7 (P= 0.021, 95%CI 1.2-6.2) and 5.3 (P= < 0.0001, 95%CI 2.4-11.7) respectively. The prognostic value of KIR3DS1 however, was greatest in patients in whom the ligand for the corresponding inhibitory KIR3DL1, Bw4 was missing. KIR3DS1+ KIR3DL1+ HLA-Bw4 negative patients had significantly reduced median EFS of 400d (315-495) vs 615 (545-684) for all other patients (P=0.048). Again this was most striking in good risk patients. Patients who had the genotype KIR3DS1+ KIR3DL1+ HLA-Bw4 –ve had a significantly shorter EFS survival of 372 days compared to 509 days in KIR3DS1+KIR3DL1+HLA-Bw4+ patients and 793 days for KIR3DS1 negative individuals (P=0.004). In conclusion: Our data from 190 patients with MM suggests that KIR3DS1, a gene previously linked to an increase risk of progression to invasive cervical carcinoma, independently predicts for poor EFS and OS following ASCT. A significant proportion (30%) of patients who are defined as good risk at ASCT (CR and PR) are KIR3DS1+ve and have an EFS which is not significantly different from patients who have refractory/relapsed disease at ASCT. This effect of KIR3DS1 is more significant in the absence of HLA-Bw4, the ligand for the inhibitory receptor KIR3DL1. The mechanism for this is effect is unclear and we are currently performing functional studies to further understand these findings. Disclosures: Apperley: Novartis: Consultancy, Honoraria. Marin:Novartis: Consultancy, Research Funding.
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Saunders, Philippa M., Phillip Pymm, Gabriella Pietra, Victoria A. Hughes, Corinne Hitchen, Geraldine M. O’Connor, Fabrizio Loiacono, et al. "Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition." Journal of Experimental Medicine 213, no. 5 (April 4, 2016): 791–807. http://dx.doi.org/10.1084/jem.20152023.
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Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognizing the widest array of HLA-I ligands. These differences were further reflected in functional studies using NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005, and *015 polymorphisms are remote from the KIR3DL1–HLA-I interface, the structures of these three KIR3DL1–HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.
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Lang, Kathrin, Marie Guenther, Stefan Bentink, Alexander H. Schmidt, Gerhard Schoefl, and Vinzenz Lange. "P108 Phased whole-gene characterization of novel KIR3DL1 , KIR3DL2 , and KIR3DL3 alleles using a dual redundant sequencing strategy." Human Immunology 78 (September 2017): 133. http://dx.doi.org/10.1016/j.humimm.2017.06.168.
Full textDissertations / Theses on the topic "KIR3DL1"
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Sene, Reginaldo Vieira. "Análise fenotípica e funcional comparativa de diferentes genótipos de KIR, com ênfase em conteúdo gênico, KIR3DL2 e KIR3DL1 na presença e ausência dos ligantes HLA-A*03/A*11 e HLA-Bw4." reponame:Repositório Institucional da UFPR, 2013. http://hdl.handle.net/1884/35235.
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Resumo: Receptores de células natural killer semelhantes à imunoglobulina (KIR) são expressos por células natural killer (NK) e subtipos de células T. Os genes KIR são altamente polimórficos e este complexo poligênico exibe variação em número de genes ativadores e inibidores, o que regula a atividade de células NK. Moléculas HLA de classe I servem como ligantes para KIR. As interações dos loci de KIR e HLA são importantes para o reconhecimento de alvos pelas células NK. Vários estudos de associação indicam que estes loci estão envolvidos em doenças infecciosas, desordens autoimunes/inflamatórias, câncer e reprodução. Dados funcionais suportam o mecanismo baseado na ação de receptores inibidores e ativadores através de diferentes combinações de genótipos KIR-HLA em doenças. A doença autoimune pênfigo vulgar (PV) é uma desordem bolhosa que afeta a pele em múltiplas camadas, causada por autoanticorpos contra desmogleína 1 e 3, já foi previamente associada com KIR. Neste estudo nós sugerimos que indivíduos KIR3DL2*001+ KIR3DL1+ e baixa frequência de genes ativadores em seu genótipo, exibem uma maior inibição de citotoxicidade quando na presença dos ligantes HLA-A*03/A*11 e HLA-Bw4. Resultados in vitro demonstraram que o cultivo de células NK de diferentes indivíduos com células T CD3 expressando HLA-A*03/A*11 e HLA-Bw4, levou a uma diminuição de citotoxicidade. Isto foi observado em indivíduos saudáveis e pacientes de pênfigo. O bloqueio com anticorpo anti-KIR3DL2 mostrou um aumento da citotoxicidade, corroborando para o potencial efeito inibidor deste gene nesta situação. Além disso, nós verificamos uma maior frequência de células NK (subtipo CD56bright) no sangue periférico de pacientes de PV quando comparado com indivíduos saudáveis. Estes dados em conjunto com a detecção de níveis aumentados de IL-6 e IFN-? nos ensaios de cultivo, contribuem para o entendimento e o papel de células NK na patogênese de pênfigo.
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Barthen, Charlotte Celine. "Nanometre-scale organisation of the inhibitory human natural killer cell receptor KIR3DL1 and its HLA class I ligands." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/61484.
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Natural killer (NK) cells express an array of activating and inhibitory receptors, which enable the detection of stress-induced markers and ‘self’ human leukocyte antigen (HLA) class I molecules on target cells. The distribution of these receptors at the cell surface is thought to be important for signal integration at the immune synapse. Killer-cell immunoglobulin-like receptors (KIR) and HLA class I proteins are highly polymorphic. In particular, allelic variation affecting the expression and function of the inhibitory receptor KIR3DL1 and its HLA class I ligands, can influence HIV infection outcome. It is not known, however, if genetic variation can affect the organisation of KIR and HLA proteins at the cell surface and at the NK-cell immune synapse. Here, single-molecule localisation microscopy was used to investigate the spatial distribution of KIR3DL1 and HLA class I proteins within the plasma membrane. HLA class I proteins were relatively evenly distributed at the nanometre-scale, with fewer than 5% of molecules forming clusters in unstimulated primary B cells. In contrast, over half of KIR3DL1 receptors were constitutively arranged in clusters sized 4064 ± 384 nm2, at the surface of resting NK cells. Receptor ligation induced the reorganisation of KIR3DL1, resulting in the formation of larger and denser clusters. Interestingly, the extent of these changes varied for different alleles of KIR3DL1, suggesting that genetic variability may affect KIR3DL1 recruitment at the NK-cell synapse. Allelic variation did not influence the constitutive organisation of KIR and HLA proteins, when expressed at the same level. However, their nanoscale distribution was influenced by cell surface levels; at higher expression levels, HLA class I clustering decreased, whereas the number of KIR3DL1 clusters increased when expressed at higher levels. These results demonstrate the distinct nanoscale organisation of KIR3DL1 and HLA class I molecules. Moreover, factors that influence their expression, including genetic variation, may have an important impact on the distribution of KIR3DL1 and HLA class I proteins at the cell surface.
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Townsley, Elizabeth. "CD8+ T Cell and NK Responses to a Novel Dengue Epitope: A Possible Role for KIR3DL1 in Dengue Pathogenesis: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/709.
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Variation in the sequence of T cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T cell responses during second heterologous infections contributing to pathology following DENV infection. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein, NS126-34. We predicted higher frequencies of NS126-34-specific CD8+ T cells in PBMC from individuals undergoing secondary, rather than primary, DENV infection due to the expansion of memory CD8+T cells. We generated a tetramer against this epitope (B57-NS126-34TET) and used it to assess the frequencies and phenotype of antigen-specific T cells in samples from a clinical cohort of children with acute DENV infection established in Bangkok, Thailand. High tetramer-positive T cell frequencies during acute infection were seen in only 1 of 9 subjects with secondary infection. B57-NS126-34-specific, other DENV epitope-specific CD8+ T cells, as well as total CD8+ T cells, expressed an activated phenotype (CD69+ and/or CD38+) during acute infection. In contrast, expression of CD71 was largely limited to DENV-specific CD8+ T cells. In vitro stimulation of CD8+ T cell lines, generated against three different DENV epitopes, indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides with substantial upregulation of CD71 detected to peptides which also elicited strong functional responses. CD71 may therefore represent a useful marker of antigenspecific T cell activation.
During the course of our analysis we found substantial binding of B57-NS126-34 TET to CD8- cells. We demonstrated that the B57-NS126-34 TET bound KIR3DL1, an inhibitory receptor on natural killer (NK) cells. NK sensitive target cells presenting the NS126-34 peptide in the context of HLA-B57 were able to dampen functional responses of only KIR3DL1+ NK cells. Analysis of the activation of an NK enriched population in our Thai cohort revealed peak activation during the critical time phase in patients with severe dengue illness, dengue hemorrhagic fever, compared to people with mild illness.
Our data identified CD71 as biologically useful marker to study DENV-specific CD8+ T cell responses and highlighted the role of viral peptides in modulating NK cell activation through KIR-MHC class I interactions during DENV infection.
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Townsley, Elizabeth. "CD8+ T Cell and NK Responses to a Novel Dengue Epitope: A Possible Role for KIR3DL1 in Dengue Pathogenesis: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/709.
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Variation in the sequence of T cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T cell responses during second heterologous infections contributing to pathology following DENV infection. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein, NS126-34. We predicted higher frequencies of NS126-34-specific CD8+ T cells in PBMC from individuals undergoing secondary, rather than primary, DENV infection due to the expansion of memory CD8+T cells. We generated a tetramer against this epitope (B57-NS126-34TET) and used it to assess the frequencies and phenotype of antigen-specific T cells in samples from a clinical cohort of children with acute DENV infection established in Bangkok, Thailand. High tetramer-positive T cell frequencies during acute infection were seen in only 1 of 9 subjects with secondary infection. B57-NS126-34-specific, other DENV epitope-specific CD8+ T cells, as well as total CD8+ T cells, expressed an activated phenotype (CD69+ and/or CD38+) during acute infection. In contrast, expression of CD71 was largely limited to DENV-specific CD8+ T cells. In vitro stimulation of CD8+ T cell lines, generated against three different DENV epitopes, indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides with substantial upregulation of CD71 detected to peptides which also elicited strong functional responses. CD71 may therefore represent a useful marker of antigenspecific T cell activation.
During the course of our analysis we found substantial binding of B57-NS126-34 TET to CD8- cells. We demonstrated that the B57-NS126-34 TET bound KIR3DL1, an inhibitory receptor on natural killer (NK) cells. NK sensitive target cells presenting the NS126-34 peptide in the context of HLA-B57 were able to dampen functional responses of only KIR3DL1+ NK cells. Analysis of the activation of an NK enriched population in our Thai cohort revealed peak activation during the critical time phase in patients with severe dengue illness, dengue hemorrhagic fever, compared to people with mild illness.
Our data identified CD71 as biologically useful marker to study DENV-specific CD8+ T cell responses and highlighted the role of viral peptides in modulating NK cell activation through KIR-MHC class I interactions during DENV infection.
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Patah, Poliana Alves. "Análise do perfil imunofenotípico das células NK e sua correlação com a expressão de PD-1 e PD-L1 em indivíduos infectados pelo HIV." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-06022017-152423/.
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A evolução do conhecimento sobre o HIV e seus efeitos sobre as diferentes células do sistema imune possibilitaram a criação e o aperfeiçoamento de um grande arsenal terapêutico. Atualmente, a sobrevida de casos recém- diagnosticados é medida em décadas; entretanto, alguns pacientes não apresentam recuperação do sistema imune após a agressão inicial sofrida pelo vírus, a despeito de tratamento adequado. As células NK são identificadas como componentes da imunidade inata, responsáveis pelo combate a infecções virais e tumores. Elas são divididas em CD56dim e CD56hi, com diferentes capacidades citotóxicas e de produção de citocinas; uma terceira subpopulação composta por células CD56neg está presente em proporções mínimas em adultos saudáveis, porém tem maior importância em neonatos e está expandida em indivíduos cronicamente infectados pelo HIV, podendo ser identificada pelos marcadores CD7 e CD16. Dentre diversos outros, as células NK expressam receptores ativadores e inibitórios chamados KIR, que interagem com moléculas HLA, identificando células próprias e aquelas que reduzem sua expressão como mecanismo de escape imunológico; a interação entre KIR e HLA tem papel na evolução clínica da infecção por HIV/AIDS, particularmente envolvendo o receptor KIR3DL1. PD- 1 é um checkpoint do sistema imunológico que pode ter sua expressão aumentada em tumores e infecções virais crônicas. A expressão de PD-1 em células T correlaciona-se a marcadores prognósticos na infecção por HIV/AIDS; sua expressão em células NK já foi documentada, porém temos poucas informações a respeito. Este trabalho buscou detalhar a expressão de PD-1 e seu ligante PD-L1 em células NK e monócitos em participantes infectados pelo HIV e controles. Foram recrutados participantes diagnosticados e acompanhados desde a infecção aguda, participantes diagnosticados após um intervalo de tempo desconhecido desde a soroconversão e controles não infectados sob alto risco por exposição sexual. As amostras foram processadas a fresco no LIM-60; PD-1 e outros marcadores foram analisados por citometria de fluxo multicor. A expressão de PD-1 em células NK correlacionou-se a contagens de células T CD4+ e expressão de PD-1 em células T nos participantes infectados; dentre estes, os participantes seguidos desde a infecção aguda tiveram menor expressão de PD-1. Os participantes seguidos desde a infecção aguda tiveram ainda menor expressão de PD-L1 em monócitos quando comparados aos participantes diagnosticados em fase desconhecida da doença, e também quando comparados aos controles não infectados. Houve aumento expressivo da proporção de células KIR3DL1+ entre as células CD56neg nos participantes infectados em comparação ao grupo não infectado. Concluímos que a expressão de PD-1 em células NK está aumentada em pessoas infectadas pelo HIV e correlaciona-se a outros parâmetros imunológicos, como contagem de células T CD4+ e expressão de PD-1 em células T. A exaustão das células NK pode, portanto, contribuir para o dano imunológico causado pelo HIV e pode ser explorada como um alvo para novas modalidades terapêuticasThe expansion of our knowledge about the HIV and its effects on the entire immune system has led the development of a vast therapeutic arsenal. Survival for newly diagnosed cases is now measured in decades;? some patients, however, never recover full immune function following the initial aggression inflicted by HIV, despite adequate treatment. NK cells are identified as innate immunity components, responsible for fighting viral infections and tumors. They are separated in CD56dim and CD56hi cells, which present different cytotoxicity and cytokine production capacity. A third distinct subpopulation constituted by CD56neg cells can be found in minimal counts in healthy adults, but is present in newborns and is expanded in chronically HIV- infected subjects;? these cells can be identified as CD7+CD16+. Among others, NK cells express activating and inhibitory receptors called KIR, which interact with HLA molecules and identify \"self\" cells and cells that have downregulated its expression as an immunologic evasion strategy. Studies have documented the importance of KIR and HLA interaction in HIV/AIDS infection clinical course, particularly involving the receptor KIR3DL1. PD-1 is an immune checkpoint that can be upregulated by tumors and chronic viral infections. PD- 1 expression on T cells is correlated to prognostic factors in HIV/AIDS infection; NK cells have been shown to express it, but further information is necessary. This study aimed at investigating PD-1 and its ligand PD-L1 expression on NK and monocytes in HIV-infected participants and controls. We recruited a group of participants who were diagnosed during acute phase of HIV infection and have been followed ever since, a group of participants who were diagnosed after unknown interval since seroconversion, and a group of uninfected controls who have a high risk due to sexual exposure. Samples were freshly processed at LIM-60; PD-1 and other markers were analyzed by multicolor flow cytometry. We found PD-1 expression on NK cells was correlated to T CD4+ cell counts and PD-1 expression on T cells, in infected participants; among them, participants followed since acute infection expressed less PD-1. They also expressed less PD-L1 in monocytes, as compared to participants diagnosed after unknown interval since seroconversion, as well as compared to the uninfected group. We found significant increase in proportion of KIR3DL1-expressing cells among CD56neg cells in infected participants compared to the uninfected group. We concluded that PD-1 expression on NK cells is increased in people infected by HIV and correlated to other immunologic parameters such as T CD4+ counts and PD-1 expression on T cells. NK cell exhaustion may, therefore, contribute to the immune damage induced by HIV-1 infection and can be also explored as a target to find new ways to restore antiviral immunity
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Zawacka, Anna [Verfasser]. "HLA-B27 subtypes differentially associated to an autoimmune disease : analysis of peptide display and attempt to define their recognition pattern by the Killer cell Ig-like receptor KIR3DL1 / Anna Zawacka." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/1023624214/34.
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Dourado, Renata Montoro. "A diversidade alélica do gene KIR3DL2 e o seu impacto nos níveis de expressão gênica deferencial." reponame:Repositório Institucional da UFPR, 2017. http://hdl.handle.net/1884/47595.
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Orientadora : Profª. Drª. Karin Braun PradoCoorientador : Prof. Dr. Danillo G. Augusto
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Genética. Defesa: Curitiba, 28/03/2017
Inclui referências : f. 92-102
Resumo: A familia de genes KIR (do ingles, killer cell immunoglobulin-like receptors) desempenha um papel central na imunidade inata e adaptativa e seu polimorfismo tem sido associado a suscetibilidade diferencial a diversas doencas. Esses genes exibem extensa variabilidade, tanto em termos de ausencia e presenca de genes, quanto em nivel alelico. Os receptores codificados por esses genes sao expressos na superficie das celulas NK e de alguns subtipos de celulas T e podem transduzir sinais ativadores ou inibidores. Pouco se conhece a respeito dos seus niveis de expressao genica diferencial, tampouco dos mecanismos de regulacao. O gene KIR3DL2 codifica um receptor inibidor e e o segundo gene KIR mais polimorfico e polialelico do complexo, com mais de 80 alelos descritos. O objetivo desse trabalho foi analisar se o polimorfismo alelico de KIR3DL2 impacta na sua expressao genica diferencial. Para isso, caracterizamos a diversidade alelica de KIR3DL2 em uma populacao de euro-descendentes de Curitiba e regiao metropolitana (n = 235), atraves de sequenciamento de DNA. As frequencias genotipicas estavam de acordo com as esperadas pelo equilibrio de Hardy-Weinberg, sendo os genotipos mais comuns: 3DL2*001/007 (11,5%), 3DL2*001/002 (6,8%) e 3DL2*002/007 (6,8%). Os alelos mais frequentes encontrados nessa populacao foram 3DL2*007 (21,7%), 3DL2*001 (21,3%) e 3DL2*002 (20%). Um total de 40 individuos com genotipos especificos e comuns na populacao desse estudo foram selecionados para a analise de expressao diferencial por citometria de fluxo. A analise de expressao diferencial foi realizada com os individuos portadores dos alelos mais frequentes encontrados na populacao, sendo eles: 3DL2*001, 3DL2*002, 3DL2*003, 3DL2*005, 3DL2*007, 3DL2*009, 3DL2*010 e 3DL2*011. Verificamos que o polimorfismo alelico de KIR3DL2 esta associado nao somente com niveis de expressao diferencial, mas tambem com diferentes quantidades de celulas NK que exibem KIR3DL2 em sua superficie. O alelo KIR3DL2*002 foi associado ao maior nivel de expressao de KIR3DL2 e ao maior numero de celulas NK 3DL2 positivas. Ja 3DL2*010 foi associado ao menor nivel de expressao e a menor quantidade de celulas NK com KIR3DL2 presente na superficie celular. Alem disso, demonstramos que um polimorfismo na regiao 3' UTR, na posicao 16545A>G (rs1865095) marca os niveis de expressao de KIR3DL2. Sugerimos que esta expressao diferencial possa estar relacionada a ligacao de miRNAs nesta regiao, especificamente o miR-2114-3p. A presenca de ligantes especificos (HLA-A3, -A11 e -B27) nao esta associada a diferentes niveis de expressao de KIR3DL2 (p = 0,5739) nem a diferentes quantidades de celulas NK KIR3DL2 positivas (p = 0,7772). Alem disso, nenhuma correlacao foi encontrada entre a expressao diferencial dos alelos de KIR3DL2 e a expressao diferencial dos alelos de HLA-A. Como perspectivas futuras pretendemos analisar, atraves de co-cultivo celular, a atividade citotoxica das celulas NK de individuos com diferentes genotipos homozigotos, como KIR3DL2*001/KIR3DL2*001, KIR3DL2*002/KIR3DL2*002, KIR3DL2*007/KIR3DL2*007 e KIR3DL2*010/KIR3DL2*010 a fim de corroborar as hipoteses geradas. Palavras-chave: Celulas NK, KIR3DL2, variabilidade alelica, HLA-A3, HLA-A11, HLA-B27, expressao diferencial.
Abstract: The KIR (killer cell immunoglobulin-like receptors) gene family plays a central role in innate and adaptive immunity and has been associated with differential susceptibility to diseases. Besides the uncommon presence and absence polymorphism that occurs in KIR, these genes also exhibit an extensive allelic variation. The receptors encoded by these genes are expressed on the surface of NK cells and on some subset of T cells. They can transduce either activating or inhibiting signals. The differential expression levels and the mechanisms of genetic regulation of these receptors are poorly known. The KIR3DL2 gene encodes an inhibitory receptor and it is one of the most polymorphic and polyallelic KIR, with more than 80 alleles described so far. This study aimed to analyze if there are a profound impact of KIR3DL2 allelic polymorphism on its differential gene expression. Allelic diversity of KIR3DL2 was characterized in an euro-descendant population from Curitiba and metropolitan region, state of PR (n = 235), by sequencing-based typing. Genotype frequencies were in accordance with Hardy-Weinberg equilibrium and the most frequent genotype was 3DL2*001/007 (11.5%), followed by 3DL2*001/002 (6.8%) and 3DL2*002/007 (6.8%). The most frequent alleles in the population were 3DL2*007 (21.7%), 3DL2*001 (21.3%) and 3DL2*002 (20%). A total of 40 individuals with specific and commom genotypes were selected for differential expression analysis by flow citometry. The differential expression analysis was made for the most common alleles found in the population: 3DL2*001, 3DL2*002, 3DL2*003, 3DL2*005, 3DL2*007, 3DL2*009, 3DL2*010 and 3DL2*011. We verified that the allelic polymorphism of KIR3DL2 was associated not only with the differential expression but also with the different amount of NK cells that display KIR3DL2 on their surface. KIR3DL2*002 allele was associated with higher expression of KIR3DL2 and higher number of KIR3DL2 positive NK cells, while KIR3DL2*010 was related to the lowest expression and lowest level of KIR3DL2 positive NK cells. It has also been found that a polymorphism in the 3' UTR, 16545A>G (rs1865095), was associated with KIR3DL2 differential expression level. We suggest that it may be related to miRNAs binding, specifically miR-2114-3p. The presence of specific HLA class I ligands (HLA-A3, -A11 and -B27) was not associated with KIR3DL2 differential expression levels (p = 0.5739) nor with different amount of NK KIR3DL2+ cells (p = 0.7772). In addition, no correlation was found between the differential expression of the KIR3DL2 alleles and the differential expression of the HLA-A alleles. As future perspectives, it is intended to analyze the citotoxic activity of NK cells from individuals with different genotypes like KIR3DL2*001/KIR3DL2*001, KIR3DL2*002/KIR3DL2*002, KIR3DL2*007/KIR3DL2*007 and KIR3DL2*010/KIR3DL2*010 through co-culture to corroborate the hypotheses generated. Key-words: NK cells, KIR3DL2, allelic variability, HLA-A3, HLA-A11, HLA-B27, differential expression.
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Sako, Nouhoum. "Lymphome NK/T et lymphomes T cutanés : Recherche et analyse de marqueurs fonctionnels (HACE1, CD 160 et KIR3DL2) : Implication de marqueurs biologiques dans la physiopathologie." Paris 7, 2014. http://www.theses.fr/2014PA077231.
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Les lymphomes T sont des maladies souvent agressives, de mauvais pronostic et résistantes aux traitements actuels. Dans la première partie de ce travail, j'ai étudié l'implication possible dans la physiopathologie du lymphome NK/T extra ganglionnaire de type nasal d'un gène suppresseur de tumeur potentiel (HACE1) associé à la délétion fréquente observée en 6q21. Les études ont montré que HACE1 (une E3 ubiquitine ligase), impliquée dans la régulation de plusieurs protéines importantes dans la biologie cellulaire, est sous exprimée au niveau transcrit (ARNm) chez ces malades et les lignées cellulaires. Par un faisceau d'arguments, j'ai montré que HACE1, bien qu'il soit sous exprimé au niveau ARNm, présente une protéine en quantité suffisante et parfaitement fonctionnelle. J'ai également montré que la surexpression de la protéine HACE1 dans les lignées de lymphome T n'a pas de conséquences ni sur la survie, ni la prolifération cellulaire. J'ai réorienté notre projet de recherche, à la suite de ces résultats, en défaveur de HACE1, sur les études de certains marqueurs NK (CD160, KIRDL2) retrouvés sur les cellules tumorales des lymphomes T cutanés. Le KIR3DL2 et le CD160 sont des marqueurs récepteurs CMH-I respectivement inhibiteur et activateur des cellules NK. Dans cette deuxième partie, j'ai identifié une population de cellules T dans la peau normale qui exprime ces deux marqueurs et pourrait être l'origine de la cellule tumorale dans le lymphome cutané. Mes résultats m'ont également permis d'émettre l'hypothèse de l'évolution de l'expression de ces 2 marqueurs avec le CD160 un marqueur des stades précoces et le KIR3DL2 un marqueur des stades tardifs du mycosis fongoïdeT-cell lymphomas are aggressive diseases with resistance to current treatments and poor prognosis. In the first part of this work, I studied the possible involvement of tumor suppressor gene (HACE1) associated with the common deletion observed in 6q21 in the pathogenesis of NK / T extra nodal nasal type lymphoma (NKTCL). Research has shown that HACE1 (an E3 ubiquitin ligase), involved in the regulation of many important cellular proteins, is down expressed at the transcript level (mRNA) in these patients and cell Unes. By a range of argument, I showed that the endogenous protein of HACE1 is in fact present in sufficient quantities and functional. I also showed that overexpression of HACE1 protein in NKTCL cells Unes has no effect on either survival or cell proliferation. I refocused my research project on the study of some NK markers (CD160, KIR3DL2) found on cutaneous T cell lymphomas. The KIR3DL2 and CD160 are respectively MCH I inhibitor or activator receptor of NK cell. In this second part, I have identified a population of T cells CD4+ CD160+ KIR3DL2+ in normal skin, which could be the origin of cutaneous lymphoma. My results demonstrate that CD160 and KIR3DL2 are two important markers for cutaneous lymphocytes
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Ghazi, Bouchra. "Réponses cellulaires associées au récepteur KIR3DL2, marqueur spécifique des lymphocytes T tumoraux du syndrome de Sézary." Thesis, Paris Est, 2012. http://www.theses.fr/2012PEST0068.
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Le syndrome de Sézary (SS) est un variant leucémique et érythrodermique de lymphomes T cutanés épidermotropes. Son diagnostic repose à la fois sur des critères cliniques, la présence de lymphocytes T à noyau atypique cérébriforme sur un frottis sanguin et la mise en évidence dans la peau, les ganglions et le sang d’un clone lymphocytaire T CD4+. Notre laboratoire a identifié KIR3DL2 comme premier marqueur membranaire spécifique des cellules tumorales de Sézary. KIR3DL2 peut ainsi être utilisé pour le diagnostic et le suivi des patients atteints du SS. Toutefois, aucune étude n’a démontré de lien entre sa structure de récepteur inhibiteur et sa fonction dans les lymphocytes tumoraux de Sézary, et plus particulièrement son implication possible dans les mécanismes régulant la prolifération et/ou la résistance à l’apoptose des cellules tumorales.Au cours de ce travail deux axes ont été développés :- Un premier axe visant à mieux comprendre la fonction de KIR3DL2 et les mécanismes de signalisation intracellulaire initiés lors de son engagement par l’anticorps AZ158 dans les lymphocytes T tumoraux de Sézary. Nos résultats mettent en évidence un rôle de corécepteur inhibiteur pour KIR3DL2 dans les cellules tumorales de Sézary. En effet, l’engagement de KIR3DL2 inhibe la prolifération et l’AICD induites par la stimulation CD3, cette inhibition étant corrélée à une modulation négative des signaux médiés par le TCR. Ainsi, KIR3DL2 ne se comporte pas comme une unité de signalisation indépendante dans les cellules tumorales de Sézary, contrairement à ce qui est observé dans les cellules NK.- Un second axe portant sur l’évaluation d’une nouvelle fonction de KIR3DL2 comme récepteur pour les ODN CpG. Ainsi, nous rapportons pour la première fois un effet direct de l’ODN CpG sur les cellules tumorales T CD4+ de Sézary. En effet, nous avons observé un effet apoptotique de l’ODN CpG-C caspases-dépendant sur les lignées et les cellules tumorales circulantes. De plus, le traitement des cellules tumorales de patients Sézary avec l’ODN CpG-C conduit à une inhibition de l’activation constitutive du facteur de transcription STAT3.La réalisation de cette étude a permis de mieux comprendre la fonction et les mécanismes initiés à partir de KIR3DL2 dans les cellules tumorales T CD4+ de Sézary. De plus, ce travail ouvre de nouvelles perspectives thérapeutiques basées sur le ciblage direct et spécifique des cellules tumorales de Sézary pouvant être associé à une stimulation des acteurs immuns grâce à l’action des ODN CpGSézary syndrome (SS) is an aggressive leukemic and erythrodermic variant of cutaneous T-cell lymphoma. It is characterized by the presence of a clonal CD4+ T lymphocyte population in the skin, lymph nodes and peripheral blood. Our laboratory has previously identified the NK cell receptor KIR3DL2 as a valuable diagnostic and prognostic marker for the detection of the tumoral T cell burden of Sézary syndrome patients. However, the function of this receptor on the malignant T lymphocyte population remained unexplored. The specific expression of KIR3DL2 by SS patients malignant cells prompted us to investigate its possible influence on mechanisms regulating the tumoral cells outgrowth and apoptosis process.To this aim, two axes were developed. The first axis aimed to highlight the function of KIR3DL2 on the malignant T lymphocyte population and to elucidate the intracellular signaling mechanisms initiated by engagement of the receptor with the monoclonal antibody AZ158. Our results show that KIR3DL2 can exert an inhibitory co-receptor function in malignant Sézary cells. Indeed, triggering of KIR3DL2 inhibits the CD3-mediated proliferation and cell death of the CD4+ KIR3DL2+ cells, this inhibition being correlated to a down-modulation of the TCR-mediated signals. Thus, KIR3DL2 does not behave as an independent signaling unit in Sézary cells, unlike NK cells.The second axis aimed to evaluate a new function of KIR3DL2 as CpG ODN receptor. We show for the first time a direct effect of CpG ODN on tumoral CD4+ T Sézary cells. Thus, we observed a caspase-dependent apoptotic effect of CpG ODN-C on Sézary cell lines and circulating malignant T cells. This process of cellular death is correlated to a dephosphorylation of the transcription factor STAT3, which is found constitutively phosphorylated and activated in Sézary cells.This study has provided new insights into the function and the intracellular signaling pathways initiated by KIR3DL2 in malignant Sézary T cells. Furthermore, this work opens new therapeutic perspectives based on the direct and specific targeting of tumor cells that could be associated to immune cell stimulation through the use of ODN CpG
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Ortonne, Nicolas. "Caractérisation phénotyque et fonctionnelle de l'expression de CD158k/KIR3DL2 à la surface des cellules néoplasiques du syndrome de Sézary." Paris 7, 2008. http://www.theses.fr/2008PA077056.
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Le syndrome de Sézary (SS) est un lymphome T cutané qui se caractérise par la prolifération dans le sang et la peau de lymphocytes T néoplasiques CD4+, appelés cellules de Sézary (CS). Nous avons montré que les CS expriment le récepteur p140/CD158k/KIR3DL2, de la famille des KIR (killer immunoglobulin-like receptor). L'expression membranaire de ce récepteur permet de caractériser les clones lymphocytaires T néoplasiques présents dans le sang des malades, identifiés par la technique de l'immunoscope, et de les distinguer de clones réactionnels. Dans la peau, l'expression transcriptionnelle de KIR3DL2 analysée par RT-PCR quantitative permet de faire le diagnostic différentiel avec les dermatoses inflammatoires érythrodermiques, et de caractériser la présence de cellules néoplasiques résiduelles dans la peau au stade débutant ou lors de rémissions partielles sous traitement. Si KIR3DL2 est le seul récepteur KIR exprimé de façon récurrente, d'autres KIR peuvent être exprimés par les CS. Nous avons montré dans la lignée de CS P1 que ces récepteurs sont fonctionnels, et que l'engagement de récepteurs activateurs (KIR2DS2 et 2DS3) favorise la prolifération cellulaire associée à la stimulation du CD3, en activant la voie de JNK, via une molécule adaptatrice encore non identifiée, alors que le récepteur inhibiteur KIR3DL2 l'inhibe. En l'absence d'anomalies génomique récurrente portant sur le locus des KIR, en position 19q13. 4, les mécanismes moléculaires conduisant à l'expression de récepteurs KIR par les CS restent inconnus. De même, le rôle de ces récepteurs, notamment de KIR3DL2, en terme de résistance à l'apoptose des cellules néoplasiques, reste à évaluerSezary syndrome (SS) is a cutaneous T-cell lymphoma characterized by the proliferation in the skin and blood of neoplastic T CD4+ lymphocytes, usually named Sezary cells (SC). We have shown that SC express the p140/CD158k/KIR3DL2 receptor of the KIR (killer immunoglobulin-like receptor) family. The cell surface expression of KIR3DL2 allows to characterize the malignant T-cell clones in the blood of patients, previously identified by the analysis of TCR Vbeta transcripts expression (immunoscope technique), and to differentiate them from reactive clones. In the skin, analysis of KIR3DL2 transcripts expression with quantitative RT-PCR allows to distinguish between SS and benign erythrodermic inflammatory dermatoses, and to identify the presence of neoplastic cells at early phases of the disease or at the time of partial remission, in the absence of circulating SC. Although KIR3DL2 appears to be the sole KIR receptor to be recurrently expressed by SC, other KIR can be present at their surface. We have shown in the SS cell line P1 that these receptors are functional, and that engagement of activatory forms (KIR2DS2 et 2DS3) enhances cell proliferation triggered by CD3 stimulation, by the recruitment of the JNK pathway through a yet unknown adaptatory molecule, whereas KIR3DL2 acts as an inhibitory receptor. In the absence of known genomic abnormality of the 19q13. 4 KIR locus, the molecular mechanisms underlying the expression of KIR by SC remains to be clarified. Further, the role of KIR, especially KIR3DL2, in the résistance of CS to apoptosis needs to be investigated
Book chapters on the topic "KIR3DL1"
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F., Nicole, Carlos Melendez-Pena, Philomena Kamya, Christos M., Mohamed-Rachid Boulassel, Jean-Pierre Routy, Rejean Thomas, et al. "Natural Killer Cells from HIV Infected Slow Progressors Who Carry the Protective HLA-B*27 Allele and Inhibitory KIR3DL1 Receptors Have Elevated Poly-Functional Potential Compared to Bw6 Homozygotes." In HIV Infection in the Era of Highly Active Antiretroviral Treatment and Some of Its Associated Complications. InTech, 2011. http://dx.doi.org/10.5772/22827.
Full textConference papers on the topic "KIR3DL1"
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Chan, Daniel C., Zhiyong Zhang, Hong Wang, Xiaomei Sui, Tiffany T. Chan, Natalie Ahn, Lewis L. Lanier, and Paul A. Bunn. "Abstract 1357: Role of Natural Killer-cell Immunoglobulin-like receptors KIR2DL1 and KIR3DL1 in immune resistance." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-1357.
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Forlenza, Christopher J., Jeanette E. Boudreau, Junting Zheng, Glenn Heller, Nai-Kong V. Cheung, and Katharine C. Hsu. "Abstract 2459: KIR3DL1 and HLA-B subtype combinations predict the efficacy of 3F8 monoclonal antibody therapy for neuroblastoma." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2459.
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Saruhan Direskeneli, G., FA Uyar, A. Cefle, S. Celebi Onder, M. Inanc, L. Ocal, and A. Gul. "THU0022 Kir3Dl1 (nkb1) and cd94 expression on peripheral blood t cells, nk cells and nkt cells in behcet’s disease." In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.531.
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Chester, Cariad, Sean Lim, Anne Marie-Cardine, Naren Rajasekaran, Hélène Sicard, Youn Kim, and Holbrook Kohrt. "Abstract 2473: KIR3DL2 is a novel target for antibody-therapy of T cell lymphomas." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2473.
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Marie-Cardine, Anne, Nicolas Viaud, Arnaud Dujardin, Rachel Joly, Laurent Gauthier, Cecile Bonnafous, Mathieu Blery, et al. "Abstract 651:Ex vivoandin vivocharacterization of IPH4102, a humanized anti-KIR3DL2 antibody for the treatment of cutaneous T-cell lymphomas." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-651.
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Viaud, Nicolas, Nathalie Granier, Stephanie Zerbib, Arnaud Dujardin, Cecile Bonnafous, Mathieu Blery, Carine Paturel, et al. "Abstract 4733: Novel therapeutic and diagnostic antibodies against KIR3DL2, a unique tumor antigen overexpressed on subtypes of T Cell Lymphomas ." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-4733.
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