Organization and sequences of the variable, joining and constant region genes of the human T-cell receptor α-chain

An essential property of the immune system is its ability to generate great diversity in antibody and T-cell immune responses. The genetic and molecular mechanisms responsible for the generation of antibody diversity have been investigated during the past several years^1,2. The gene for the variable (V) region, which determines antigen specificity, is assembled when one member of each of the dispersed clusters of V gene segments, diversity (D) elements (for heavy chains only) and joining (J) segments are fused by DNA rearrangement^1-3. The cloning of the β-chain of the T-cell antigen receptor^4,5 revealed that the organization of the β-chain locus, which is similar to that of immunoglobulin genes ^6-12, is also composed of noncontiguous segments of V^7-9, D^10,11, J^6,9,11 and constant (C) region genes ^6-12. The structure of the α-chain seems to consist of a V and a C domain connected by a J segment^13-16. We report here that the human T-cell receptor α-chain gene consists of a number of noncontiguous V and J gene segments and a C region gene. The V region gene segment is interrupted by a single intron, whereas the C region contains four exons. The J segments, situated 5′ of the C region gene, are dispersed over a distance of at least 35 kilobases (kb). Signal sequences, which are presumably involved in DNA recombination, are found next to the V and J gene segments.