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

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Abstract
Human T-cell receptor .beta.-chain (Ti.beta.) genes are formed by the rearrangement of varible (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 displayed 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 a 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).