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

Abstract

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. 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. The cloning of the beta-chain of the T-cell antigen receptor revealed that the organization of the beta-chain locus, which is similar to that of immunoglobulin genes, is also composed of noncontiguous segments of V, D, J and constant (C) region genes. The structure of the alpha-chain seems to consist of a V and a C domain connected by a J segment. We report here that the human T-cell receptor alpha-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.

Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor.

“…It contains 14 codons for a hydrophobic leader, followed by an 3308 intron of 143 bp and Vca exon of 97 codons. The sequence of the J region, and downstream from it, is identical to the published Ja (Yoshikai et al, 1985) which is the third one from CX ( Figure 1). …”

“…The Ta chain locus consists of -50-100 Va gene segments separated by an unknown distance from at least 20 joining (Ja) gene segments which are dispersed over > 60 kb of DNA upstream of a single Ca gene segment Davis, 1985;Yoshikai et al, 1985;Winoto et al, 1985). Diversification of Ta may result from germline diversity of many genes, combinatorial joining allowing random association of V and J genes and junctional diversity due to imprecise joining and addition of extra nucleotides to the V -J junction.…”

Regulation of T-cell antigen receptor (TCR) alpha-chain expression by TCR beta-chain transcripts.

“…Thus, the downregulation must involve intronic sequences or the 5' or 3' untranslated regions of the a-chain transcripts. Intriguingly, the 3' untranslated region of a-chain mRNA is conserved among species, not only at the sequence level but also in the unusual feature of bearing an intron (25)(26)(27). A regulatory pathway involving the 5' region of /3-chain transcripts and the 3' untranslated region of a-chain transcripts would be an attractive model for the present observations.…”

Non-T, non-B acute lymphocytic leukemias: Cellular origin based on molecular analyses of immunoglobulin and T-cell .ALPHA.- and .BETA.-chain receptor gene rearrangements.

“…Difficulty of detecting rearrangement of TcRa genes depends on the inherent structure of the a-chain gene. The /3-chain gene differs from the a-chain gene in that there is only one constant region and there are more than 20 J segments covered over more than 50 kb upstream of the constant region (Harday et al 1985;Winoto et al 1985;Yoshikai et al 1985). As rearrangement occurs into any one of the J segments over a region of more than 50 kb, the use of probes to the constant region generally do not detect rearrangement.…”