T-cell receptors in immune responses
T lymphocytes play a central role in the generation of both humoral and cell-mediated immune responses. Although T-cells mediate diverse effector functions, most recognize antigenic peptide presented by molecules encoded within the major histocompatibility complex (MHC). The fine specificity of a T-cell is determined by a heterodimeric receptor for antigen (TCR) displayed on the cell surface. The TCR present on the majority of T-cells is composed of an alpha and a beta chain which are similar to immunoglobulins (Ig) in both sequence and gene organization. Genes for the alpha and beta chains of the TCR are encoded in germline DNA as discontinuous gene segments that rearrange specifically in T-cells during development. The variable regions of each of these chains are responsible for antigen recognition and are encoded by juxtaposed variable (V), diversity (D) (for beta chains), and joining (J) gene segments (reviewed in Toyonaga and Mak, 1987; Wilson et al., 1988; Davis and Bjorkman, 1988). A critical difference between TCR and Ig is that somatic mutation does not appear to play a role in the generation of TCR diversity (Ikuta et al., 1985), which emphasizes the importance of germline polymorphism of TCR gene segments. Knowledge of both the extent and variability of the germline TCR repertoire is critical to understanding the diversity of potential T-cell specificities.
KeywordsMajor Histocompatibility Complex Gene Segment Major Histocompatibility Complex Gene Beta Chain Major Histocompatibility Complex Antigen
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