The T cells leaving the thymus are functional cells expressing unique and specific T-cell receptors (TCRs) that are both tolerant to self-antigens and restricted to self-MHC ( 14). This ensures that only those T cells that are self-tolerant survive while eliminating the self-reactive T cells. During this selection, T cells bearing TCR with a high affinity for self-peptide Major Histocompatibility Complexes (MHC) undergo apoptosis (negative selection), whereas those bearing low-affinity TCR for self-peptides survive and differentiate into mature T cells (positive selection). T cell development is largely dependent on T cell receptor interactions which facilitates the transition of double positive T cell progenitors (CD4+ and CD8+) to single positive cells (CD4+ or CD8+) after thymal selection. During T cell development, T cell precursors travel to the thymus, where they develop into mature T cells and are exported to the periphery where they can be activated by antigens and differentiate into effector and memory cells. T cells are key mediators in mounting an effective cell mediated immune response. In this review, we will be focusing on antigen-specificity in the context of T cells and their TCRs and discussing it in detail. The wide diversity of T cell phenotypes is a direct result of the wide repertoire of T cell receptors (TCR) and range of T cell antigen-specificities. However, other CD4 Th cell subsets, such as the Th1*, especially in the context of mycobacterial infection ( 10– 12), and Th9 and Th22 subsets that release IL-9 and IL-22, have become more well-known in recent years ( 13). There are several different CD4 T helper (Th) subsets that have been found, but the Th1, Th2, and Th17 lineages are the most well-known. Both CD4 and CD8 T cells differentiate into independent memory cell lineages that release various and frequently mutually exclusive sets of cytokines in response to antigen contact and the proper co-stimulatory cues ( 8, 9). Unlike CD4 T cells, which normally focus on protein antigens sourced from the extracellular environment, CD8 T cells preferentially identify antigens that are biosynthesized by infected or altered host cells. These effector cells include the CD4 and CD8 lineage. T cell phenotypes range from highly cytotoxic effector cells to regulatory T cells that fight inflammation. This broad range of functions is enabled by the diversity of T cell phenotypes and antigen specificities. T cells are also critical effector cells for providing protection against wide range of pathogens and cancer, as well as maintaining self-tolerance. While B cells are responsible for antibody mediated responses, T cells disseminate their action via a plethora of cell mediated responses ( 7). Upon antigen-specific activation individual T and B cells undergo clonal expansion to produce a population of identical antigen-reactive cells ( 4– 6). These cells have a diverse and finely tuned repertoire of receptors with the ability to discriminate between self and non-self-antigens ( 2, 3). The adaptive response, a crucial component of the immune system, relies on antigen-specificity, and mediates action via B and T cells ( 1). The innate and adaptive arm of the immune system work in coordination to elicit host immune responses against a variety of pathogens. Setting the stage: T cell mediated immunity Further, we discuss how these methods have been applied to study the TCR repertoire in various diseases in order to characterize the antigen-specific T cells involved in the immune control of disease. Here, we discuss the published approaches to studying antigen-specific T cells and their specific TCR repertoire. As a result, many studies have leveraged TCR sequencing in an attempt to elucidate the role of antigen-specific T cells in various contexts. Importantly, high-throughput TCR sequencing provides a fingerprint which allows tracking of specific T cells and their clonal expansion in response to particular antigens. ![]() T cell receptors (TCRs) mediate the antigen-specificities found in T cells. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United StatesĪntigen-specific T cells play a central role in the adaptive immune response and come in a wide range of phenotypes.Chihab, Kendall Kearns, Sloan Lewis, Sudhasini Panda, Lisa Willemsen, Julie G.
0 Comments
Leave a Reply. |