1 - Genomic Organization of the T Cell Receptor

Abstract

A majority of T cells recognize antigens by means of a T cell receptor (TcR) composed of either alpha-beta (alpha beta) or gamma-delta (gamma delta) chains. These TcR genes are members of the immunoglobulin gene superfamily. This family includes the major histocompatibility complex (MHC) genes, whose products are essential for recognitions of foreign antigens by the TcR. This phenomenon is known as MHC restriction. All the TcR chains have similar protein structures consisting of extracellular variable and constant domains, intracellular cytoplasmic tails, and a hydrophobic transmembrane region with several potential N-linked glycosylation sites. On the cell surface, the TcR heterodimers are found to be associated with the CD3 complex. This CD3 complex which is composed of at lease four chains (CD3 gamma, CD3 delta, CD3 epsilon, and CD3 zeta) is thought to be responsible for the transduction of antigen-binding signal through the cell membrane to facilitate the appropriate T cell function. The germline TcR genes are composed of noncontiguous variable (V), diversity (D), joining (J), and constant (C) gene segments. During T cell ontogeny, these VDJ or VJ gene segments rearrange to form a TcR gene encoding a unique variable domain, which is then joined to the C region sequences by RNA splicing following transcription. This process of rearrangement allows the generation of large numbers of new and unique TcR genomic structures, before a primary transcript can be made. In this review article, we summarize the recent findings on the genomic organization of these TcR genes in both the human and murine systems.