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 years1,2. 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 rearrangement1-3. The cloning of the β-chain of the T-cell antigen receptor4,5 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 V7-9, D10,11, J6,9,11 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 segment13-16. 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.
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