Journal articles: 'T-cell receptor'

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Y, Elshimali. "Chimeric Antigen Receptor T-Cell Therapy (Car T-Cells) in Solid Tumors, Resistance and Success." Bioequivalence & Bioavailability International Journal 6, no. 1 (2022): 1–6. http://dx.doi.org/10.23880/beba-16000163.

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CARs are chimeric synthetic antigen receptors that can be introduced into an immune cell to retarget its cytotoxicity toward a specific tumor antigen. CAR T-cells immunotherapy demonstrated significant success in the management of hematologic malignancies. Nevertheless, limited studies are present regarding its efficacy in solid and refractory tumors. It is well known that the major concerns regarding this technique include the risk of relapse and the resistance of tumor cells, in addition to high expenses and limited affordability. Several factors play a crucial role in improving the efficacy of immunotherapy, including tumor mutation burden (TMB), microsatellite instability (MSI), loss of heterozygosity (LOH), the APOBEC Protein Family, tumor microenvironment (TMI), and epigenetics. In this minireview, we address the current and future applications of CAR T-Cells against solid tumors and their measure for factors of resistance and success.

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Robbins, Paul F. "T-Cell Receptor–Transduced T Cells." Cancer Journal 21, no. 6 (2015): 480–85. http://dx.doi.org/10.1097/ppo.0000000000000160.

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Sowka, Slawomir, Roswitha Friedl-Hajek, Ute Siemann, Christof Ebner, Otto Scheiner, and Heimo Breiteneder. "T Cell Receptor CDR3 Sequences and Recombinant T Cell Receptors." International Archives of Allergy and Immunology 113, no. 1-3 (1997): 170–72. http://dx.doi.org/10.1159/000237537.

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Akatsuka, Yoshiki. "IV. T-cell Receptor-engineered T Cells." Nihon Naika Gakkai Zasshi 108, no. 7 (2019): 1384–90. http://dx.doi.org/10.2169/naika.108.1384.

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Moskalev, Alexander V., Boris Yu Gumilevskiy, Vasiliy Ya Apchel, and Vasiliy N. Cygan. "T-cell receptor family, signal transduction, and transcription factors in T-cell immune response." Bulletin of the Russian Military Medical Academy 27, no. 1 (2025): 135–46. https://doi.org/10.17816/brmma636850.

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This study investigated signal transduction in T-lymphocytes, whose cell receptors are categorized into several groups based on their signaling mechanisms and the intracellular biochemical pathways they activate, including modular signaling proteins and adapter molecules that perform scaffolding or catalytic functions. Adapter proteins facilitate signaling complexes by linking various enzymes. Immune receptors, which are composed of integral membrane proteins from the immunoglobulin superfamily, interact with specific tyrosine-containing motifs within transmembrane signaling proteins in their cytoplasmic domains. The intensity of T-cell receptor signaling influences the development and activation of T-lymphocytes. Signal transduction is regulated by coreceptor activation and suppressed by inhibitory receptors. The interaction between T-cell receptors and major histocompatibility complex molecules induces coreceptor clustering and tyrosine phosphorylation of immunoreceptor tyrosine-based activation motifs within the cluster of differentiation 3 complex. Protein and lipid phosphorylation is a key regulatory mechanism in T-cell receptor and coreceptor signaling. Activated zeta-chain-associated protein kinase 70 phosphorylates adapter proteins, promoting interactions with downstream signaling molecules. G-proteins stimulate mitogen-activated protein kinases, which activate transcription factors. Phospholipase C activates T-cell transcription factors, resulting in enhanced gene transcription. T-cell receptor signal modulation is mediated by protein tyrosine phosphatases, which dephosphorylate tyrosine residues on signaling proteins, inhibiting T-cell receptor-mediated signal transduction.

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Rabin, Ronald L., Matthew K. Park, Fang Liao, Ruth Swofford, David Stephany, and Joshua M. Farber. "Chemokine Receptor Responses on T Cells Are Achieved Through Regulation of Both Receptor Expression and Signaling." Journal of Immunology 162, no. 7 (1999): 3840–50. http://dx.doi.org/10.4049/jimmunol.162.7.3840.

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Abstract To address the issues of redundancy and specificity of chemokines and their receptors in lymphocyte biology, we investigated the expression of CC chemokine receptors CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4 and responses to their ligands on memory and naive, CD4 and CD8 human T cells, both freshly isolated and after short term activation in vitro. Activation through CD3 for 3 days had the most dramatic effects on the expression of CXCR3, which was up-regulated and functional on all T cell populations including naive CD4 cells. In contrast, the effects of short term activation on expression of other chemokine receptors was modest, and expression of CCR2, CCR3, and CCR5 on CD4 cells was restricted to memory subsets. In general, patterns of chemotaxis in the resting cells and calcium responses in the activated cells corresponded to the patterns of receptor expression among T cell subsets. In contrast, the pattern of calcium signaling among subsets of freshly isolated cells did not show a simple correlation with receptor expression, so the propensity to produce a global rise in the intracellular calcium concentration differed among the various receptors within a given T cell subset and for an individual receptor depending on the cell where it was expressed. Our data suggest that individual chemokine receptors and their ligands function on T cells at different stages of T cell activation/differentiation, with CXCR3 of particular importance on newly activated cells, and demonstrate T cell subset-specific and activation state-specific responses to chemokines that are achieved by regulating receptor signaling as well as receptor expression.

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Kamiya, Takahiro, Desmond Wong, Yi Tian Png, and Dario Campana. "A novel method to generate T-cell receptor–deficient chimeric antigen receptor T cells." Blood Advances 2, no. 5 (2018): 517–28. http://dx.doi.org/10.1182/bloodadvances.2017012823.

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Key Points Newly designed PEBLs prevent surface expression of T-cell receptor in T cells without affecting their function. Combined with chimeric antigen receptors, PEBLs can rapidly generate powerful antileukemic T cells without alloreactivity.

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Rosenberg, Kenneth M., and Nevil J. Singh. "Subset-specific neurotransmitter receptor expression tunes T cell activation." Journal of Immunology 200, no. 1_Supplement (2018): 47.22. http://dx.doi.org/10.4049/jimmunol.200.supp.47.22.

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Abstract T cells continually patrol and invade other tissues and are exposed to varying tissue-specific cues. Different tissues are typically innervated by neurons using characteristic neurotransmitters. Therefore, encounter with particular neurotransmitters has the potential to influence the tissue-specific behavior of T cells. Although neurons utilize a complex array of over 180 neurotransmitter receptor (NR) genes, we find that murine T cells in total express only a limited set (26 detected) of them. Furthermore, the expression is T cell subset-specific suggesting distinct functional roles. Several receptors, including Adrb2, Gabrr2, and Chrnb2, are most highly expressed in naïve CD4 T cells while CD8 T cells specifically express the glutamate receptor Gria3 and have high expression of the cannabinoid receptor Cnr2. Within the CD4 population, memory T cells upregulate Hrh4 and P2ry1 while the VIP receptor Vipr1 is uniquely absent from regulatory T cells. In order to understand how these distinct patterns affect immune responses, we are analyzing the functional impact of signaling T cells through them. Importantly, NR signaling pathways considerably overlap with T cell receptor (TCR) signaling pathways. Accordingly, preliminary data shows that a competing signal from NR receptors such as the β2 adrenergic, histamine H2, and VPAC1 (VIP) receptors dampens direct T cell activation through the CD3 complex. Determining how T cells integrate the complex contextual information they encounter in vivo guides our understanding of T cell decision making and will allow for the development of more targeted therapeutics.

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OMOTO, K., Y. Y. KONG, K. NOMOTO та ін. "Sensitization of T-cell receptor-αβ+ T cells recovered from long-term T-cell receptor downmodulation". Immunology 88, № 2 (1996): 230–37. http://dx.doi.org/10.1111/j.1365-2567.1996.tb00009.x.

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Grunewald, Johan, Ylva Kaiser, Mahyar Ostadkarampour, et al. "T-cell receptor–HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis." European Respiratory Journal 47, no. 3 (2015): 898–909. http://dx.doi.org/10.1183/13993003.01209-2015.

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In pulmonary sarcoidosis, CD4+ T-cells expressing T-cell receptor Vα2.3 accumulate in the lungs of HLA-DRB1*03+ patients. To investigate T-cell receptor-HLA-DRB1*03 interactions underlying recognition of hitherto unknown antigens, we performed detailed analyses of T-cell receptor expression on bronchoalveolar lavage fluid CD4+ T-cells from sarcoidosis patients.Pulmonary sarcoidosis patients (n=43) underwent bronchoscopy with bronchoalveolar lavage. T-cell receptor α and β chains of CD4+ T-cells were analysed by flow cytometry, DNA-sequenced, and three-dimensional molecular models of T-cell receptor-HLA-DRB1*03 complexes generated.Simultaneous expression of Vα2.3 with the Vβ22 chain was identified in the lungs of all HLA-DRB1*03+ patients. Accumulated Vα2.3/Vβ22-expressing T-cells were highly clonal, with identical or near-identical Vα2.3 chain sequences and inter-patient similarities in Vβ22 chain amino acid distribution. Molecular modelling revealed specific T-cell receptor-HLA-DRB1*03-peptide interactions, with a previously identified, sarcoidosis-associated vimentin peptide, (Vim)429–443 DSLPLVDTHSKRTLL, matching both the HLA peptide-binding cleft and distinct T-cell receptor features perfectly.We demonstrate, for the first time, the accumulation of large clonal populations of specific Vα2.3/Vβ22 T-cell receptor-expressing CD4+ T-cells in the lungs of HLA-DRB1*03+ sarcoidosis patients. Several distinct contact points between Vα2.3/Vβ22 receptors and HLA-DRB1*03 molecules suggest presentation of prototypic vimentin-derived peptides.

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Sommermeyer, Daniel, Julia Neudorfer, Monika Weinhold, et al. "Designer T cells by T cell receptor replacement." European Journal of Immunology 36, no. 11 (2006): 3052–59. http://dx.doi.org/10.1002/eji.200636539.

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Meeks, Christian Matthew, and Christopher G. Horton. "Modulation of CD4+ T cell polarization using non-canonical co-receptors." Journal of Immunology 198, no. 1_Supplement (2017): 150.15. http://dx.doi.org/10.4049/jimmunol.198.supp.150.15.

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Abstract CD4+ T helper cells are a diverse group of cells promoting target cell death and production of antibodies. These cells acquire one of several fates following signals through the T cell receptor, co-receptors, and cytokines. The cytokine requirements inducing the polarization of T cell fate has been heavily evaluated and reasonably well defined. However, the influence provided by co-receptors has not been completely elucidated. Traditionally, in vitro T cell polarization assays utilize CD28 stimulation as the primary co-receptor signal required for differentiation. Others have observed the importance of supplementary co-receptors in activation of T helper cells, though little is known about their function in early stage polarization. We hypothesized that the addition of signaling through supplemental co-receptors would alter T helper cell polarization. To conduct these studies, we isolated naïve T cells and polarized them towards Th1 or Tfh fates in the presence or absence of recombinant B7-DC Fc chimera or recombinant B7-H4 Fc chimera. We observed a significant and selective alteration in T helper cell polarization in the presence of these non-canonical co-receptors. These data suggest a complex interplay between cytokine and co-receptor signals that cooperate for robust Th cell polarization. Furthermore, these findings illustrate the potential for novel mechanisms of T cell manipulation for vaccine design and treatment of T cell-mediated diseases.

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Simon, Bianca, Dennis C. Harrer, Beatrice Schuler-Thurner, Gerold Schuler, and Ugur Uslu. "Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer." Cancers 11, no. 5 (2019): 696. http://dx.doi.org/10.3390/cancers11050696.

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Tumor cells can develop immune escape mechanisms to bypass T cell recognition, e.g., antigen loss or downregulation of the antigen presenting machinery, which represents a major challenge in adoptive T cell therapy. To counteract these mechanisms, we transferred not only one, but two receptors into the same T cell to generate T cells expressing two additional receptors (TETARs). We generated these TETARs by lentiviral transduction of a gp100-specific T cell receptor (TCR) and subsequent electroporation of mRNA encoding a second-generation CSPG4-specific chimeric antigen receptor (CAR). Following pilot experiments to optimize the combined DNA- and RNA-based receptor transfer, the functionality of TETARs was compared to T cells either transfected with the TCR only or the CAR only. After transfection, TETARs clearly expressed both introduced receptors on their cell surface. When stimulated with tumor cells expressing either one of the antigens or both, TETARs were able to secrete cytokines and showed cytotoxicity. The confirmation that two antigen-specific receptors can be functionally combined using two different methods to introduce each receptor into the same T cell opens new possibilities and opportunities in cancer immunotherapy. For further evaluation, the use of these TETARs in appropriate animal models will be the next step towards a potential clinical use in cancer patients.

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Barber, Amorette. "103 Inclusion of a Dap10 costimulatory domain enhances anti-tumor efficacy of chimeric PD1-expressing T cells in multiple types of solid tumors." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A114. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0103.

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BackgroundAdoptive transfer of T cells is a promising anti-tumor therapy for many cancers. To enhance tumor recognition by T cells, chimeric antigen receptors (CAR) consisting of signaling domains fused to receptors that recognize tumor antigens can be expressed in T cells. One receptor that is a prospective target for a new chimeric antigen receptor is PD1 because the ligands for the PD1 receptor are expressed on many cancer types. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 receptor extracellular domain and the activation domain of CD3 zeta. In addition, current chimeric antigen receptor therapies utilize various costimulatory domains to enhance anti-tumor efficacy. Therefore, we also compared the inclusion of CD28, Dap10, 4-1BB, GITR, ICOS, or OX40 costimulatory domains in the chPD1 receptor to determine which costimulatory domain induced optimal anti-tumor immunity.MethodsTo determine if this novel CAR could potentially target a wide variety of tumors, the anti-tumor efficacy of chPD1 T cells against murine lymphoma, melanoma, kidney, pancreatic, liver, colon, breast, ovarian, prostate, and bladder cancer cell lines was measured.ResultsOf the eighteen cell lines tested, all expressed PD1 ligands on their cell surface, making them potential targets for chPD1 T cells. Regardless of the costimulatory domain in the CAR, all of the chPD1 T cells induced similar levels of T cell proliferation and tumor cell lysis. However, differences were observed in the cytokine secretion profiles depending on which costimulatory receptor was included in the CAR. While most of the chPD1 T cell receptor combinations secreted both pro-inflammatory (IFNγ, TNFα, IL-2, GM-CSF, IL-17, and IL-21) and anti-inflammatory cytokines (IL-10), chPD1 T cells containing a Dap10 costimulatory domain secreted high levels of proinflammatory cytokines but did not secrete a significant amount of anti-inflammatory cytokines. Furthermore, T cells expressing chPD1 receptors with a Dap10 domain also had the strongest anti-tumor efficacy in vivo. ChPD1 T cells did not survive for longer than 14 days in vivo, however treatment with chPD1 T cells induced long-lived protective host-anti-tumor immune responses in tumor-bearing mice.ConclusionsTherefore, adoptive transfer of chPD1 T cells could be a novel therapeutic strategy to treat multiple types of cancer and inclusion of the Dap10 costimulatory domain in chimeric antigen receptors may induce a preferential cytokine profile for anti-tumor therapies.Ethics ApprovalThe study was approved by Longwood University’s IACUC.

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Robson MacDonald, H., Rosemary K. Lees, and Werner Held. "Developmentally Regulated Extinction of Ly-49 Receptor Expression Permits Maturation and Selection of NK1.1+ T Cells." Journal of Experimental Medicine 187, no. 12 (1998): 2109–14. http://dx.doi.org/10.1084/jem.187.12.2109.

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Clonally distributed inhibitory receptors negatively regulate natural killer (NK) cell function via specific interactions with allelic forms of major histocompatibility complex (MHC) class I molecules. In the mouse, the Ly-49 family of inhibitory receptors is found not only on NK cells but also on a minor (NK1.1+) T cell subset. Using Ly-49 transgenic mice, we show here that the development of NK1.1+ T cells, in contrast to NK or conventional T cells, is impaired when their Ly-49 receptors engage self-MHC class I molecules. Impaired NK1.1+ T cell development in transgenic mice is associated with a failure to select the appropriate CD1-reactive T cell receptor repertoire. In normal mice, NK1.1+ T cell maturation is accompanied by extinction of Ly-49 receptor expression. Collectively, our data imply that developmentally regulated extinction of inhibitory MHC-specific receptors is required for normal NK1.1+ T cell maturation and selection.

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Mekala, Divya J., and Terrence L. Geiger. "Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes." Blood 105, no. 5 (2005): 2090–92. http://dx.doi.org/10.1182/blood-2004-09-3579.

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AbstractWe developed an approach that increases CD4+CD25+ regulatory T-cell potency by antigen-specifically redirecting them against pathologic T lymphocytes. The regulatory cells are transgenically modified with chimeric receptors that link antigen–major histocompatibility complex (MHC) extracellular and transmembrane domains with the cytoplasmic signaling tail of T-cell receptor ζ (TCR-ζ). The receptors' antigen-MHC recognizes the TCR of cognate T lymphocytes. Receptor engagement stimulates the receptor-modified T cell (RMTC) through the linked ζ chain. CD4+CD25+ RMTCs expressing a myelin basic protein (MBP) 89-101-IAs-ζ receptor, unlike unmodified CD4+CD25+ T cells or CD4+CD25- RMTCs, prevented and treated experimental allergic encephalomyelitis (EAE) induced with MBP89-101. The RMTCs were effective even after the autoreactive T-cell repertoire had diversified to include specificities not directly targeted by the chimeric receptor. Remissions were sustained and mortality was decreased from more than 50% to 0%. These results provide proof of principal for a novel approach to enforce the interaction of regulatory and pathologic T lymphocytes, thereby facilitating the treatment of autoimmune disease.

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Zhu, Yuwen, Alessandro Paniccia, Alexander C. Schulick, et al. "Identification of CD112R as a novel checkpoint for human T cells." Journal of Experimental Medicine 213, no. 2 (2016): 167–76. http://dx.doi.org/10.1084/jem.20150785.

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T cell immunoglobulin and ITIM domain (TIGIT) and CD226 emerge as a novel T cell cosignaling pathway in which CD226 and TIGIT serve as costimulatory and coinhibitory receptors, respectively, for the ligands CD155 and CD112. In this study, we describe CD112R, a member of poliovirus receptor–like proteins, as a new coinhibitory receptor for human T cells. CD112R is preferentially expressed on T cells and inhibits T cell receptor–mediated signals. We further identify that CD112, widely expressed on antigen-presenting cells and tumor cells, is the ligand for CD112R with high affinity. CD112R competes with CD226 to bind to CD112. Disrupting the CD112R–CD112 interaction enhances human T cell response. Our experiments identify CD112R as a novel checkpoint for human T cells via interaction with CD112.

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Joyce, David E., Yan Chen, Rochelle A. Erger, Gary A. Koretzky, and Steven R. Lentz. "Functional Interactions Between the Thrombin Receptor and the T-Cell Antigen Receptor in Human T-Cell Lines." Blood 90, no. 5 (1997): 1893–901. http://dx.doi.org/10.1182/blood.v90.5.1893.

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Abstract The proteolytically activated thrombin receptor (TR) is expressed by T lymphocytes, which suggests that thrombin may modulate T-cell activation at sites of hemostatic stress. We examined the relationship between TR function and T-cell activation in the Jurkat human T-cell line and in T-cell lines with defined defects in T-cell antigen receptor (TCR) function. Stimulation with thrombin or the synthetic TR peptide SFLLRN produced intracellular Ca2+ transients in Jurkat cells. As the concentration of TR agonist was increased, peak Ca2+ mobilization increased, but influx of extracellular Ca2+ decreased. TR signaling was enhanced in a TCR-negative Jurkat line and in T-cell lines deficient in the tyrosine kinase lck or the tyrosine phosphatase CD45, both of which are essential for normal TCR function. TCR cross-linking with anti-CD3 IgM desensitized TR signaling in Jurkat cells, but not in CD45-deficient cells. A proteinase-activated receptor (PAR-2)–specific agonist peptide, SLIGKV, produced small Ca2+ transients in both MEG-01 human megakaryocytic cells and Jurkat cells, but was less potent than the TR-specific agonist TFRIFD in both cell types. Like TR signaling, PAR-2 signaling was enhanced in TCR-negative or lck-deficient Jurkat clones. These findings provide evidence for functional cross-talk between proteolytically activated receptors and the TCR.

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Guilbault, Benoit, and Robert J. Kay. "RasGRP1 Sensitizes an Immature B Cell Line to Antigen Receptor-induced Apoptosis." Journal of Biological Chemistry 279, no. 19 (2004): 19523–30. http://dx.doi.org/10.1074/jbc.m314273200.

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RasGRP1 is a guanine nucleotide exchange factor that activates Ras GTPases and is activated downstream of antigen receptors on both T and B lymphocytes. Ras-GRP1 provides signals to immature T cells that confer survival and proliferation, but RasGRP1 also promotes T cell receptor-mediated deletion of mature T cells. We used the WEHI-231 cell line as an experimental system to determine whether RasGRP1 can serve as a quantitative modifier of B cell receptor-induced deletion of immature B cells. A 2-fold elevation in RasGRP1 expression markedly increased apoptosis of WEHI-231 cells following B cell receptor ligation, whereas a dominant negative mutant of RasGRP1 suppressed B cell receptor-induced apoptosis. Activation of ERK1 or ERK2 kinases was not required for RasGRP1-mediated apoptosis. Instead, elevated RasGRP1 expression caused down-regulation of NF-κB and Bcl-xL, which provide survival signals counter-acting apoptosis induction by B cell receptor. Inhibition of NF-κB was sufficient to enhance B cell receptor-induced apoptosis of WEHI-231 cells, and ligation of co-stimulatory receptors that activate NF-κB suppressed the ability of RasGRP1 to promote B cell receptor-induced apoptosis. These experiments define a novel apoptosis-promoting pathway leading from B cell receptor to the inhibition of NF-κB and demonstrate that differential expression of RasGRP1 has the potential to modulate the sensitivities of B cells to negative selection following antigen encounter.

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Huang, Jun. "Lattice light-sheet microscopy Multi-Dimensional Analyses (LaMDA) of T-cell receptor dynamics predict T-cell signaling states." Journal of Immunology 204, no. 1_Supplement (2020): 80.10. http://dx.doi.org/10.4049/jimmunol.204.supp.80.10.

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Abstract Cell surface receptors dynamically change in response to cell signaling, but a direct linkage between receptor dynamics and cell state has not been established. Here we report the development of lattice light-sheet microscopy multi-dimensional analyses (LaMDA), a pipeline that combines high spatiotemporal-resolution four-dimensional lattice light-sheet microscopy, machine learning, and diffusion maps to analyze T-cell receptor (TCR) dynamics and predict T-cell signaling states without the need for complex biochemical measurements. LaMDA images thousands of TCR microclusters on the surface of live primary cells to collect high-dimensional dynamic data for machine learning, which extracts key dynamic features to build predictive diffusion maps. LaMDA spatiotemporally reveals global changes of TCRs across the 3D cell surface, accurately differentiates stimulated cells from unstimulated cells, precisely predicts attenuated T-cell signaling after CD4 and CD28 receptor blockades, and reliably discriminates between structurally similar TCR ligands. We anticipate broad usage of this approach for other receptors and cells, as well as for guiding the design and development of future immunotherapies for cancer, infection, and autoimmunity.

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Lin, Joseph, and Arthur Weiss. "T cell receptor signalling." Journal of Cell Science 114, no. 2 (2001): 243–44. http://dx.doi.org/10.1242/jcs.114.2.243.

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Ray, L. Bryan. "T cell receptor dynamics." Science 373, no. 6550 (2021): 71.4–72. http://dx.doi.org/10.1126/science.373.6550.71-d.

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Marrack, P., and J. Kappler. "The T cell receptor." Science 238, no. 4830 (1987): 1073–79. http://dx.doi.org/10.1126/science.3317824.

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McGargill, Maureen A., and Kristin A. Hogquist. "T cell receptor editing." Immunology Letters 75, no. 1 (2000): 27–31. http://dx.doi.org/10.1016/s0165-2478(00)00282-0.

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Mak, T. W. "T cell antigen receptor." Leukemia Research 10, no. 1 (1986): 84. http://dx.doi.org/10.1016/0145-2126(86)90120-7.

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Potter, C. "The T-Cell Receptor." Journal of Clinical Pathology 42, no. 3 (1989): 334. http://dx.doi.org/10.1136/jcp.42.3.334-a.

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HAUSER, STEPHEN L. "T-Cell Receptor Genes." Annals of the New York Academy of Sciences 756, no. 1 T-Cell Recept (1995): 233–40. http://dx.doi.org/10.1111/j.1749-6632.1995.tb44521.x.

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Lieberman, Judy, and David H. Raulet. "T cell gamma receptor." Immunologic Research 6, no. 4 (1987): 288–93. http://dx.doi.org/10.1007/bf02935523.

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Padovan, E., G. Casorati, P. Dellabona, S. Meyer, M. Brockhaus, and A. Lanzavecchia. "Expression of two T cell receptor alpha chains: dual receptor T cells." Science 262, no. 5132 (1993): 422–24. http://dx.doi.org/10.1126/science.8211163.

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MELMS, A., J. R. OKSENBERG, G. MALCHEREK, et al. "T-Cell Receptor Gene Usage of Acetylcholine Receptor-specific T-Helper Cells." Annals of the New York Academy of Sciences 681, no. 1 Myasthenia Gr (1993): 313–14. http://dx.doi.org/10.1111/j.1749-6632.1993.tb22904.x.

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Alcázar, Isabela, Miriam Marqués, Amit Kumar та ін. "Phosphoinositide 3–kinase γ participates in T cell receptor–induced T cell activation". Journal of Experimental Medicine 204, № 12 (2007): 2977–87. http://dx.doi.org/10.1084/jem.20070366.

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Class I phosphoinositide 3–kinases (PI3Ks) constitute a family of enzymes that generates 3-phosphorylated polyphosphoinositides at the cell membrane after stimulation of protein tyrosine (Tyr) kinase–associated receptors or G protein–coupled receptors (GPCRs). The class I PI3Ks are divided into two types: class IA p85/p110 heterodimers, which are activated by Tyr kinases, and the class IB p110γ isoform, which is activated by GPCR. Although the T cell receptor (TCR) is a protein Tyr kinase–associated receptor, p110γ deletion affects TCR-induced T cell stimulation. We examined whether the TCR activates p110γ, as well as the consequences of interfering with p110γ expression or function for T cell activation. We found that after TCR ligation, p110γ interacts with Gαq/11, lymphocyte-specific Tyr kinase, and ζ-associated protein. TCR stimulation activates p110γ, which affects 3-phosphorylated polyphosphoinositide levels at the immunological synapse. We show that TCR-stimulated p110γ controls RAS-related C3 botulinum substrate 1 activity, F-actin polarization, and the interaction between T cells and antigen-presenting cells, illustrating a crucial role for p110γ in TCR-induced T cell activation.

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Zhang, Peng-Fei, Chuang Wang, Le Zhang, and Qiu Li. "Reversing chemokine/chemokine receptor mismatch to enhance the antitumor efficacy of CAR-T cells." Immunotherapy 14, no. 6 (2022): 459–73. http://dx.doi.org/10.2217/imt-2021-0228.

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Currently, the antitumor efficacy of chimeric antigen receptor T cells in solid tumors is modest. Both chemokines and their receptors play a key role in the proliferation of cancer cells, tumor angiogenesis, organ-selective metastasis and migration of immune cells to solid tumors. Unfortunately, frequent chemokine/chemokine receptor ‘mismatch’ between effector cells and the tumor microenvironment results in inefficient T-cell infiltration and antitumor efficacy. Thus, reversing the ‘mismatch’ of chemokines and chemokine receptors appears to be a promising method for promoting T-cell infiltration into the tumor and enhancing their antitumor efficacy. In this review, we discuss functions of the chemokine/chemokine receptor axis in cancer immunity and the current understanding, challenges and prospects for improving the effect of chimeric antigen receptor T cells by reversing the mismatch between chemokines and chemokine receptors.

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Meiliana, Anna, Nurrani Mustika Dewi, and Andi Wijaya. "CAR T Cells: Precision Cancer Immunotherapy." Indonesian Biomedical Journal 10, no. 3 (2018): 203–16. http://dx.doi.org/10.18585/inabj.v10i3.635.

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BACKGROUND: Current cancer drugs and treatments are aiming at eradicating tumor cells, but often are more toxic then effective, killing also the normal cells and not selectively the tumor cells. There is good personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity, which called adoptive cell therapy (ACT). A review of the unique biology of T cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities.CONTENT: Chimeric antigen receptors (CAR) are recombinant receptors which provide both antigen-binding and T cell-activating functions. Many kind of CARs has been reported for the past few years, targeting an array of cell surface tumor antigens. Their biologic functions have extremely changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. The combination of CARs with costimulatory ligands, chimeric costimulatory receptors, or cytokines can be done to further enhance T cell potency, specificity and safety. CARs reflects a new class of drugs with exciting potential for cancer immunotherapy.SUMMARY: CAR-T cells have been arising as a new modality for cancer immunotherapy because of their potent efficacy against terminal cancers. They are known to exert higher efficacy than monoclonal antibodies and antibodydrug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors.KEYWORDS: chimeric antigen receptor, CAR T cells, adoptive cell therapy, ACT, T cell receptor, TCR, cancer, immunotherapy

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Tual, Margaux, Angélique Bellemare-Pelletier, Susan Moore, et al. "MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence." Journal for ImmunoTherapy of Cancer 13, no. 4 (2025): e011829. https://doi.org/10.1136/jitc-2025-011829.

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BackgroundChimeric antigen receptor T cell (CAR-T)-based immunotherapies have reshaped the therapeutic landscape of cancer treatment, in particular for patients afflicted with leukemia. However, defects in CAR behaviors and clinical complications have hindered their widespread application across diverse cancer types. Chief among these defects is high tonic signaling, absent in native activating immune receptors, which accelerates T cell exhaustion and undermines treatment efficacy. We hypothesized that these limitations arise because current CAR architectures fail to replicate the modular design of native activating immune receptors, which integrate distinct receptor and signaling modules. This modular assembly is crucial for maintaining proper receptor regulation and function.MethodsTherefore, we set forth to develop a modular chimeric antigen receptor leveraging the same assembly principles found in native activating immune receptors to reestablish the intrinsic safeguards in receptor expression and signaling.ResultsThe resulting Modular Actuation Receptor Complex (MARC) displayed surface expression levels akin to its native immune receptor counterpart, the NK cell receptor KIR2DS3, while eliminating tonic signaling. In a clinically relevant mouse leukemia model, MARC-T cells exhibited remarkable long-term persistence and a less exhausted phenotype compared with conventional CAR-T cells.ConclusionsWith its modular architecture, the MARC offers unparalleled opportunities for optimization and broad applicability across different cell types, paving the way for transformative advancements in cell-based therapies. This innovation holds immense promise as a next-generation therapeutic tool in clinical settings.

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Kempkes, B., E. Palmer, S. Martin, et al. "Predominant T cell receptor gene elements in TNP-specific cytotoxic T cells." Journal of Immunology 147, no. 8 (1991): 2467–73. http://dx.doi.org/10.4049/jimmunol.147.8.2467.

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Abstract H-2b class I-restricted, TNP-specific CTL clones were obtained by limiting dilution cloning of either short term polyclonal CTL lines or spleen cells of TNP-immunized mice directly ex vivo. Sequence analyses of mRNA coding for TCR alpha- and beta-chains of 11 clones derived from CTL lines from individual C57BL/6 mice revealed that all of them expressed unique but clearly nonrandom receptor structures. Five alpha-chains (45%) employed V alpha 10 gene elements, and four of those (36%) were associated with J beta 2.6-expressing beta-chains. The alpha-chains from these four TCR, moreover, contained an acidic amino acid in position 93 of their N or J region-determined sequences. Clones isolated directly from spleen cells carried these types of receptors at lower frequency, 27% V alpha 10 and 19% J beta 2.6, indicating that bulk in vitro cultivation on Ag leads to selection for these particular receptors. However, even in TNP-specific CTL cloned directly ex vivo, V alpha 10 usage was increased about fivefold over that in Ag-independently activated T cells in H-2b mice (4 to 5%). The selection for V alpha 10/J beta 2.6-expressing cells was obtained repeatedly in other TNP-specific CTL lines from C57BL/6 mice but not in FITC-specific CTL from the same strain or in TNP-specific CTL lines from B10.BR (H-2k) or B10.D2 (H-2d) mice. We conclude from this (a) that the selection for V alpha 10/J beta 2.6+ T cells is driven by the complementarity of these receptors to a combination of TNP and MHC epitopes and (b) that predominant receptor structures reflect the existence of a surprisingly limited number of "T cell-relevant" hapten determinants on the surface of covalently TNP-modified cells.

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Hansenne, I., G. Rasier, Ch Charlet-renard, et al. "Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines." Clinical and Developmental Immunology 11, no. 1 (2004): 45–51. http://dx.doi.org/10.1080/10446670410001670481.

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Abstract Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes,OTR,V1R,V2RandV3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147.OTRis transcribed in all thymic T cell subsets and T cell lines, whileV3Rtranscription is restricted to CD4+CD8+and CD8+thymic cells. NeitherV1RnorV2Rtranscripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data,OTRandV3Rare differentially expressed during T cell ontogeny. Moreover, the restriction ofOTRtranscription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment.

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Steverding, Dietmar. "Cycle Numbers of Cell Surface Recycling Receptors." Receptors 2, no. 2 (2023): 160–65. http://dx.doi.org/10.3390/receptors2020010.

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The cycle number (nc) of a recycling receptor is defined as the average number of round trips (cell surface–endosome–cell surface) the receptor can make before it is degraded. This characteristic parameter of recycling receptors can be easily determined from the receptor’s half-life (t½, the time in which 50% of the receptor is degraded) and cycling time (Tc, the time a receptor needs to complete a round trip). Relationship analyses revealed that nc increases linearly with increasing t½ and decreases exponentially with increasing Tc. For commonly observed t½ and Tc values, it was calculated that recycling receptors have nc values of <300. In addition, it was found that recycling receptors in cancer cells have generally smaller nc values (<100), whereas recycling receptors in normal cells have larger nc values (>100). Based on this latter finding, the cycle number nc may be a useful criterion for distinguishing between cancer and normal cells.

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Greenbaum, Uri, Ecaterina I. Dumbrava, Amadeo B. Biter, Cara L. Haymaker, and David S. Hong. "Engineered T-cell Receptor T Cells for Cancer Immunotherapy." Cancer Immunology Research 9, no. 11 (2021): 1252–61. http://dx.doi.org/10.1158/2326-6066.cir-21-0269.

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Abstract Engineering immune cells to target cancer is a rapidly advancing technology. The first commercial products, chimeric-antigen receptor (CAR) T cells, are now approved for hematologic malignancies. However, solid tumors pose a greater challenge for cellular therapy, in part because suitable cancer-specific antigens are more difficult to identify and surrounding healthy tissues are harder to avoid. In addition, impaired trafficking of immune cells to solid tumors, the harsh immune-inhibitory microenvironment, and variable antigen density and presentation help tumors evade immune cells targeting cancer-specific antigens. To overcome these obstacles, T cells are being engineered to express defined T-cell receptors (TCR). Given that TCRs target intracellular peptides expressed on tumor MHC molecules, this provides an expanded pool of potential targetable tumor-specific antigens relative to the cell-surface antigens that are targeted by CAR T cells. The affinity of TCR T cells can be tuned to allow for better tumor recognition, even with varying levels of antigen presentation on the tumor and surrounding healthy tissue. Further enhancements to TCR T cells include improved platforms that enable more robust cell expansion and persistence; coadministration of small molecules that enhance tumor recognition and immune activation; and coexpression of cytokine-producing moieties, activating coreceptors, or mediators that relieve checkpoint blockade. Early-phase clinical trials pose logistical challenges involving production, large-scale manufacturing, and more. The challenges and obstacles to successful TCR T-cell therapy, and ways to overcome these and improve anticancer activity and efficacy, are discussed herein.

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Radtanakatikanon, Araya, Peter F. Moore, Stefan M. Keller, and William Vernau. "Novel clonality assays for T cell lymphoma in cats targeting the T cell receptor beta, T cell receptor delta, and T cell receptor gamma loci." Journal of Veterinary Internal Medicine 35, no. 6 (2021): 2865–75. http://dx.doi.org/10.1111/jvim.16288.

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Lefrançois, Leo, Terrence A. Barrett, Wendy L. Havran та Lynn Puddington. "Developmental expression of the αIELβ7 integrin on T cell receptor γδ and T cell receptor αβ T cells". European Journal of Immunology 24, № 3 (1994): 635–40. http://dx.doi.org/10.1002/eji.1830240322.

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Janssen, O., S. Wesselborg, B. Heckl-Ostreicher, et al. "T cell receptor/CD3-signaling induces death by apoptosis in human T cell receptor gamma delta + T cells." Journal of Immunology 146, no. 1 (1991): 35–39. http://dx.doi.org/10.4049/jimmunol.146.1.35.

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Abstract mAb directed against the TCR/CD3 complex activate resting T cells. However, TCR/CD3 signaling induces death by apoptosis in immature (CD4+CD8+) murine thymocytes and certain transformed leukemic T cell lines. Here we show that anti-TCR and anti-CD3 mAb induce growth arrest of cloned TCR-gamma delta + T cells in the presence of IL-2. In the absence of exogenous IL-2, however, the very same anti-TCR/CD3 mAb stimulated gamma delta (+)-clones to proliferation and IL-2 production. In the presence of exogenous IL-2, anti-TCR/CD3 mAb induced the degradation of DNA into oligosomal bands of approximately 200 bp length in cloned gamma delta + T cells. This pattern of DNA fragmentation is characteristic for the programmed cell death termed apoptosis. These results demonstrate that TCR/CD3 signaling can induce cell death in cloned gamma delta + T cells. In addition, this report is the first to show that apoptosis triggered by TCR/CD3 signaling is not restricted to CD4+CD8+ immature thymocytes and transformed leukemic T cell lines but can be also observed with IL-2-dependent normal (i.e., TCR-gamma delta +) T cells.

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Chen, Yuehong, Jianhong Sun, Huan Liu, Geng Yin, and Qibing Xie. "Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases." Journal of Immunology Research 2019 (December 31, 2019): 1–9. http://dx.doi.org/10.1155/2019/5727516.

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Chimeric antigen receptor T (CAR-T) cells are T cells engineered to express specific synthetic antigen receptors that can recognize antigens expressed by tumor cells, which after the binding of these antigens to the receptors are eliminated, and have been adopted to treat several kinds of malignancies. Autoimmune diseases (AIDs), a class of chronic disease conditions, can be broadly separated into autoantibody-mediated and T cell-mediated diseases. Treatments for AIDs are focused on restoring immune tolerance. However, current treatments have little effect on immune tolerance inverse; even the molecular target biologics like anti-TNFα inhibitors can only mildly restore immune balance. By using the idea of CAR-T cell treatment in tumors, CAR-T cell-derived immunotherapies, chimeric autoantibody receptor T (CAAR-T) cells, and CAR regulatory T (CAR-T) cells bring new hope of treatment choice for AIDs.

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Li, Zhuqing, Maria J. Calzada, John M. Sipes та ін. "Interactions of thrombospondins with α4β1 integrin and CD47 differentially modulate T cell behavior". Journal of Cell Biology 157, № 3 (2002): 509–19. http://dx.doi.org/10.1083/jcb.200109098.

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Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both positively and negatively. We found that these opposing responses arise from interactions of TSP1 with two different T cell receptors. The integrin α4β1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and was required for stimulation of T cell adhesion, chemotaxis, and matrix metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells depended on the activation state of α4β1 integrin, and TSP1 inhibited interaction of activated α4β1 integrin on T cells with its counter receptor vascular cell adhesion molecule-1. The α4β1 integrin recognition site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence replicated the α4β1 integrin–dependent activities of TSP1. The β1 integrin recognition sites in TSP1, however, were neither necessary nor sufficient for inhibition of T cell proliferation and T cell antigen receptor signaling by TSP1. A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSP1 but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities. Modulating the relative expression or function of these two TSP receptors could therefore alter the direction or magnitude of T cell responses to TSPs.

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Biffen, M., and D. R. Alexander. "Mobilization of intracellular Ca2+ by adenine nucleotides in human T-leukaemia cells: evidence for ADP-specific and P2y-purinergic receptors." Biochemical Journal 304, no. 3 (1994): 769–74. http://dx.doi.org/10.1042/bj3040769.

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The expression of purinergic receptors on human T-cells was investigated and the receptors were shown to be functionally coupled to intracellular signals in two out of eight T-leukaemia cell-lines. Addition of adenine nucleotides resulted in mobilization of intracellular Ca2+ in HPB-ALL cells and a cell line (CB1) recently isolated from a patient with T-acute lymphoblastic leukaemia. Of a range of nucleotides tested only ADP and ATP elevated intracellular levels of Ca2+, with ADP being the more potent agonist. Ca2+ mobilization by ATP was accompanied by increased inositol phosphate production and was blocked by the purinergic receptor antagonist, Reactive Blue 2, indicating that ATP was interacting with a P2y receptor. Intracellular Ca2+ release triggered by ADP was independent of both inositol phosphate production and protein tyrosine phosphorylation. Expression of the transmembrane phosphotyrosine phosphatase, CD45, had no effect on ADP-stimulated Ca2+ mobilization. Our results show that functional P2y receptors can be expressed on T-cells, and also identify a novel T-cell ADP receptor. Signals mediated by these purinergic receptors could play important roles in modulating T-cell function.

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Hashimoto, Y., K. Yui, D. Littman, and M. I. Greene. "T-cell receptor genes in autoimmune mice: T-cell subsets have unexpected T-cell receptor gene programs." Proceedings of the National Academy of Sciences 84, no. 16 (1987): 5883–87. http://dx.doi.org/10.1073/pnas.84.16.5883.

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Young, Mary H., Garnet Navarro, Peter Askovich, and Alan Aderem. "T cell receptor signaling and Toll-like receptor signaling converge to amplify T cell responses." Journal of Immunology 196, no. 1_Supplement (2016): 128.5. http://dx.doi.org/10.4049/jimmunol.196.supp.128.5.

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Abstract Toll-like receptors (TLRs) are an essential part of the innate immune system. Their function on antigen presenting cells helps drive efficient T cell responses to pathogens. However, T cells also express several TLRs. Additionally, many of the downstream signaling components of TLRs are shared with those of the T cell receptor. Our hypothesis is that these two pathways work in concert to exert unique and potent T cell responses. We have found that several TLRs are able to enhance T cell responses, including TLR3, TLR4, TLR7, and TLR9. We have found that TLR7 signaling, in particular, synergizes with TCR activation and improves T cell effector functions. Priming T cells with synthetic and natural TLR7 ligands before TCR ligation further boosts T cell responses. The combination of TLR7 and TCR stimulation in T cells enhances cytokine production and proliferation in T cells. We identified several overlapping components between TLR7 and TCR activation pathways by gene expression, which may provide combinatorial increases in T cell activation. In addition, we found increases in anti-viral response pathways that are atypical in T cells. This response was unique to the combination of TLR and TCR stimuli. Thus, we wanted to determine if TLR7 signaling in T cells is important during an acute infection. During influenza, T cell-specific loss of TLR7 alters infection dynamics in the T cell population, resulting in significant activation delays and abnormalities. These findings show that TLR7 is important in normal T cell responses to viral infections. Understanding the contribution of TLR signaling to T cell activation will be useful in guiding enhanced vaccine strategies.

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Li, Hao-Kang, Tai-Sheng Wu, Yi-Chiu Kuo, et al. "A Novel Allogeneic Rituximab-Conjugated Gamma Delta T Cell Therapy for the Treatment of Relapsed/Refractory B-Cell Lymphoma." Cancers 15, no. 19 (2023): 4844. http://dx.doi.org/10.3390/cancers15194844.

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Chimeric antigen receptor T cell (CAR-T) therapy has been applied in the treatment of B-cell lymphoma; however, CAR-T manufacturing requires virus- or non-virus-based genetic modification, which causes high manufacturing costs and potential safety concerns. Antibody–cell conjugation (ACC) technology, which originated from bio-orthogonal click chemistry, provides an efficient approach for arming immune cells with cancer-targeting antibodies without genetic modification. Here, we applied ACC technology in Vγ9Vδ2 T (γδ2 T) cells to generate a novel off-the-shelf CD20-targeting cell therapy ACE1831 (rituximab-conjugated γδ2 T cells) against relapsed/refractory B-cell lymphoma. ACE1831 exhibited superior cytotoxicity against B-cell lymphoma cells and rituximab-resistant cells compared to γδ2 T cells without rituximab conjugation. The in vivo xenograft study demonstrated that ACE1831 treatment strongly suppressed the aggressive proliferation of B-cell lymphoma and prolonged the survival of tumor-bearing mice with no observed toxicity. Mass spectrometry analysis indicated that cell activation receptors including the TCR complex, integrins and cytokine receptors were conjugated with rituximab. Intriguingly, the antigen recognition of the ACC-linked antibody/receptor complex stimulated NFAT activation and contributed to ACE1831-mediated cytotoxicity against CD20-expressing cancer cells. This study elucidates the role of the ACC-linked antibody/receptor complex in cytotoxicity and supports the potential of ACE1831 as an off-the-shelf γδ2 cell therapy against relapsed/refractory B-cell lymphoma.

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Scheurich, P., B. Thoma, U. Ucer, and K. Pfizenmaier. "Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses." Journal of Immunology 138, no. 6 (1987): 1786–90. http://dx.doi.org/10.4049/jimmunol.138.6.1786.

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Abstract The expression of specific tumor necrosis factor (TNF) membrane receptors and biological effects of recombinant TNF (rTNF)-alpha on normal human T lymphocytes were studied. Although resting T cells lacked specific binding capacity for rTNF-alpha, high affinity (Kd 70 pM) TNF receptors were de novo induced upon primary activation of T cells. Comparison of TNF receptor expression with that of high affinity interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) receptors, respectively, revealed similarities to IL 2-receptor expression with respect to kinetics of induction. However, maximum expression of TNF receptors (approximately equal to 5000/cell at day 6) and subsequent decline occurred approximately 3 days after the peak of IL 2-receptor expression. In contrast, no change in the expression of IFN-gamma receptors (Kd 10 pM, 300 to 400 receptors/cell) was found in the course of T cell activation. On activated TNF receptor positive T cells, TNF-alpha exerted multiple stimulatory activities. Thus TNF increased the expression of HLA-DR antigens and high affinity IL 2 receptors. As a consequence, TNF-treated T cells showed an enhanced proliferative response to IL 2. Moreover, TNF-alpha was effective as a co-stimulator of IL 2-dependent IFN-gamma production. These data indicate that TNF-alpha may regulate growth and functional activities of normal T cells.

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Shimada, Shinji. "T Cell Receptor Expression by Dendritic Epidermal T Cells." Journal of Dermatology 21, no. 11 (1994): 829–32. http://dx.doi.org/10.1111/j.1346-8138.1994.tb03297.x.

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Pacholczyk, Rafal, and Joanna Kern. "The T-cell receptor repertoire of regulatory T cells." Immunology 125, no. 4 (2008): 450–58. http://dx.doi.org/10.1111/j.1365-2567.2008.02992.x.

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Journal articles on the topic 'T-cell receptor'

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