Generation of diversity of the beta chain of the human T-lymphocyte receptor for antigen

Abstract

Human T-cell receptor beta-chain (Ti beta) genes are formed by the rearrangement of variable (V), diversity (D), and joining (J) gene segments. A comparison of the nucleotide and deduced amino acid sequences of the variable regions of six human Ti beta cDNAs reveals that they display a level of homology similar to that shared by human immunoglobulin heavy chain V genes. In contrast to immunoglobulin V regions, which contain three discrete regions of hypervariability, the Ti beta V regions display a more widely distributed pattern of variability. Southern blot analyses show that most human Ti V beta gene families contain one to three members. However, a single family containing at least eight members is identified. This analysis allows the identification of at least 15 human Ti V beta germ-line genes. The sequence data show that at least one germ-line Ti beta J gene is used preferentially in Ti beta cDNAs. Moreover, they suggest the presence of at least four human germ-line Ti beta D genes. At least three mechanisms are involved in generating the diversity of human Ti beta genes: (i) the combinatorial rearrangement of different V, D, and J genes; (ii) imprecise V-D-J joining, including V-D joining in any of three translational reading frames; and (iii) the addition of extra nucleotides at the V-D-J joints (N-region diversity).