Genomic organization of the genes encoding mouse T-cell receptor α-chain

Abstract

The vertebrate immune system uses two kinds of antigen-specific receptors, the immunoglobulin molecules of B cells and the antigen receptors of T cells. T-cell receptors are formed by a combination of two different polypeptide chains, alpha and beta (refs 1-3). Three related gene families are expressed in T cells, those encoding the T-cell receptor, alpha and beta, and a third, gamma (refs 4-6), whose function is unknown. Each of these polypeptide chains can be divided into variable (V) and constant (C) regions. The V beta regions are encoded by V beta, diversity (D beta) and joining (J beta) gene segments that rearrange in the differentiating T cell to generate V beta genes. The V gamma regions are encoded by V gamma, J gamma and, possibly, D gamma gene segments. Studies of alpha complementary DNA clones suggest that alpha-polypeptides have V alpha and C alpha regions and are encoded by V alpha and J alpha gene segments and a C alpha gene. Elsewhere in this issue we demonstrate that 18 of 19 J alpha sequences examined are distinct, indicating that the J alpha gene segment repertoire is much larger than those of the immunoglobulin (4-5) or beta (14) gene families. Here we report the germline structures of one V alpha and six J alpha mouse gene segments and demonstrate that the structures of the V alpha and J alpha gene segments and the alpha-recognition sequences for DNA rearrangement are similar to those of their immunoglobulin and beta-chain counterparts. We also show that the J alpha gene-segment organization is strikingly different from that of the other immunoglobulin and rearranging T-cell gene families. Eighteen J alpha gene segments map over 60 kilobases (kb) of DNA 5' to the C alpha gene.

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

“…1) of EcoRI digested human genomic DNA wh one predominant band of 3.6 kb and three weakly c izing bands. The most closely related Va regions ar Va HAP-26 (Yoshikai et al, 1986) and the m (Winoto et al, 1985) (Figure 2) shows that the joining occurred six nucleotides after the recombination signal of the Ja and two nucleotides before the recombination signal of the Va with the addition of _~ithree unrelated nucleotides at the junction (TTG) which represent N-region (Alt and Baltimore, 1982) interest that the enhancer operated in both T cells and B cells, but not in HeLa cells. In B cells the Va promoter does not drive the expression of CAT, but when linked to the enhancer the expression of CAT is similar to that found in T cells.…”

“…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.…”

Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

“…Probes 2131 and 3131 were isolated from cosmid clone BDFL 2.5, and probes 4F1, 4F2, 6M1, 6F1, and 9F1 from cosmid clone BDFL 7.5 (32) . Probes 11M1, 11M2, and 13F1 were isolated from cosmid clone TA 28 .1 (34). Probe IOFI is a 3.0-kb Barn HI fragment isolated from the genomic (EMBL) clone 4B2A1-a-2 (35) .…”

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.…”