![]() Nevertheless, it is commonly hypothesized that such antigen-specific T cells display an exhaustion phenotype that cannot easily be reverted ( 12), especially in the contest of an immunosuppressive tumor microenvironment ( 13). The reasons for these mixed clinical results are still not fully elucidated and cannot be addressed with a simple explanation. Despite the evidence of tumor-specific T cells in cancer patients both among the tumor infiltrating lymphocytes ( 3– 5) and in the peripheral blood ( 6– 9), the presence of these cells is often not sufficient to induce cancer regressions even after checkpoint immunotherapy ( 10, 11). In the field of cancer immunotherapy, the identification not only of cancer antigens, but also of the antigen-specific TCRs, is a major research topic. The TCR also interacts with the peptide presented by the MHC molecule, mostly by specific interaction with the CDR3. The TCR needs to contact the MHC molecule on the cell surface, mostly by specific interactions with CDR1 and CDR2. Lastly, the process of antigen recognition is also complicated. The great variability of TCRs is essential to enable their unique ability to recognize antigenic targets, either pathogens or tumor cells. It is estimated that the total number of possible combination could be greater than 10 18 ( 2). It is clear that the structure of the TCR allows for great variability, which is further increased by the heterodimeric pairing of the α and β chains. the P and N nucleotides) during the process, resulting in a unique and unpredictable amino acid sequence for each CDR3 ( 1). The joining of the V(D)J regions is imprecise, and nucleotides can be lost or added (e.g. While CDR1 and CDR2 are encoded by the V segment, the CDR3 regions results from the juxtaposition of the V, (D) and J regions during somatic recombination. Within each V segment, there are three hypervariable regions, or complementarity-determining regions (CDR1, CDR2 and CDR3). In human, 42 V segments, 2 D and 12 J are identified in β chain locus and 43 V and 58 J for the α locus. The variable region of the β chain consists of three gene segments called variable (V), diversity (D) and junctional (J), but the α chain only consists of the V and J segments. In TCRα chain, there is only one constant region gene segment, Cα. In TCRβ chain, there are two constant region gene segments, Cβ1 and Cβ2, with some shared sequences. ![]() Each of the two chains is made of a variable region and a constant region that are spliced together during the T cell development that happens in the thymus. Taken together, this powerful tool not only can validate previous observation by conventional approaches, but also can pave the way for new discovery, such as previous unidentified T-cell subpopulations that potentially responsible for clinical outcomes in patients with autoimmunity or cancer.Ī T-cell receptor (TCR) is a heterodimer consisting of two chains, TCRα and TCRβ chains, that allow the recognition of peptides in the contest of major histocompatibility complex (MHC) molecules. More importantly, we discuss the applications of single-cell techniques for T-cell studies, including T-cell development and differentiation, as well as the role of T cells in autoimmunity, infectious disease and cancer immunotherapy. In addition, we summarize the approaches used for the identification of T-cell neoantigens, an important aspect for T-cell mediated cancer immunotherapy. Here, we review the single-cell techniques used for T-cell studies, including T-cell receptor (TCR) and transcriptome analysis. Recent advances on single-cell sequencing techniques have empowered scientists to discover new biology at the single-cell level. T cells have been known to be the driving force for immune response and cancer immunotherapy. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States 2Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.1Department of Laboratory Medicine, Division of Clinical Microbiology, ANA FUTURA, Karolinska Institutet, Stockholm, Sweden.
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