The T cell receptor β chain genes are located on chromosome 6 in mice and chromosome 7 in humans

Caccia, Nicolette; Kronenberg, Mitchell; Saxe, Debra; Haars, Regina; Bruns, G. A. P.; Goverman, Joan; Malissen, Marie; Willard, H.F.; Yoshikai, Yasunobu; Simon, Melvin I.; Hood, Leroy; Mak, Tak W.

doi:10.1016/0092-8674(84)90443-4

Cited by 199 publications

(73 citation statements)

References 44 publications

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“…These results indicate that genes encoding the T-cell receptor, at least the /8-chain gene, are different from Ig genes, though they most likely share a common ancestor (8). The finding that the human /3-chain variable (V) and constant (C) region genes (V and C) are located on chromosome 7 (14), where there are no Ig genes, confirmed that these genes are independent of Ig genes. These observations, coupled with the fact that a and ,B chains are approximately the same size, suggest that the a chain is probably also Ig-related and may contain similar V and C domains (8).…”

supporting

confidence: 62%

Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.

Yanagi

Chan

Chin

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

202

109

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We report the isolation and characterization of 19 classes of nonrearranging T cell-specific cDNA clones and two cDNA clones encoding the a and /3 chains of the T-cell antigen receptor from a human T-cell line, Jurkat. Results indicate that the human a-chain gene, like its /8-chain counterpart, undergoes somatic rearrangement in T cells. In addition, it shows sequence homology to its P-chain counterpart and immunoglobulin, indicating that the human a chain is also a member of the immunoglobulin supergene family. Sequence comparison suggests that the a chain also may be composed of variable (V), diversity (D), joining (J), and constant (C) region gene segments. The protein deduced from the cDNA sequence has a molecular weight of 29,995 and possesses six potential N-glycosylation sites. The availability of a-and /3-chain genes of the T-cell receptor from the same T-cell line provides tools to study their possible roles in recognition of antigens and major histocompatibility complex products by the human T-cell receptor.Antigen recognition by T lymphocytes is mediated by the T-cell antigen receptor composed of an a-and /3-chain heterodimer situated on the surface of these immunocompetent cells (1-3). About a year ago, we (4) and Hedrick et al.(5) cloned cDNAs that specified, respectively, the /3 chain of the human and mouse T-cell receptor (6). Subsequent studies have indicated that the genes encoding these structures undergo somatic rearrangement in T lymphocytes (7) and are homologous to the Ig genes (8). In addition, their genomic structures are similar, but not identical in organization, to Ig genes (9-13). These results indicate that genes encoding the T-cell receptor, at least the /8-chain gene, are different from Ig genes, though they most likely share a common ancestor (8). The finding that the human /3-chain variable (V) and constant (C) region genes (V and C) are located on chromosome 7 (14), where there are no Ig genes, confirmed that these genes are independent of Ig genes. These observations, coupled with the fact that a and ,B chains are approximately the same size, suggest that the a chain is probably also Ig-related and may contain similar V and C domains (8).In this manuscript, we report the analysis of a number of human T-cell-specific cDNA clones and describe the characterization and sequence of a human T-cell clone with homology to the a chain ofthe human T-cell antigen receptor. The results reveal that, like the /B-chain genes of the T-cell receptor (4, 5), the a-chain genes are homologous to Ig genes and undergo somatic rearrangement in T cells. While these studies were in progress, isolation of the murine a-chain cDNA (15, 16) and partial protein sequence of the human a chain (17, 18) were reported. The elucidation of the a and 83 chains of the T-cell receptor should provide the molecular tools necessary for the study of the recognition of antigens and major histocompatibility complex products by human T cells.

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supporting

confidence: 62%

Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.

Yanagi

Chan

Chin

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

202

109

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“…6 d) was of particular interest because karotypic analysis of the fresh tumor cells revealed a tandem duplication of the long arm of chromosome 7 (58,59). The TCRfl gene has been mapped to chromosome 7 (60); conflicting reports have placed the gene variously on the long and the short arm (61,62). Southern blot analysis following Bam HI digestion of DNA from primary tumor cells reveals the presence of two rearranged bands, in addition to the germline bands.…”

Section: Resultsmentioning

confidence: 99%

Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells.

Jarrett

Mitsuya

Mann

et al. 1986

The Journal of Experimental Medicine

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We studied the configuration and expression of the gene encoding the beta chain of the T cell receptor (TCR beta) in cell lines and primary tumor cells infected by the human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I). Most of the cell lines and all the primary tumor cells showed rearrangement of the TCR beta gene, and in each case the rearrangement was distinct. The majority of cases examined were clonal with respect to a particular TCR beta gene rearrangement. Primary tumor cells from one case (SD) were found to have a tandem duplication of a portion of chromosome 7; this appears to have resulted in the presence of three alleles of the TCR beta gene, each of which is arranged differently. This suggests that the chromosomal abnormality, and possibly infection by HTLV-I, occurred before TCR beta gene rearrangement. Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I. Cloned T cells of known antigen specificity that are infected by HTLV-I in vitro show impairment of immune function, including loss of antigen-specific responsiveness and the acquisition of alloreactivity. Comparison of the configuration of the TCR beta gene before and after infection revealed no changes detectable by Southern blot analysis. Levels of expression of the TCR beta gene at the mRNA level and surface expression of the T3 complex were also not significantly altered, suggesting that changes in immune function cannot be attributed to quantitative changes in the TCR molecule. The configuration of the TCR beta gene in primary tumor cells infected by HTLV-I was compared with that in the derived cell lines. In all pairs examined, the configuration in the primary tumor cells was different from that in the cell lines, strongly suggesting that the cells that grow in culture are not the original neoplastic cells.

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“…The results, (Table 1) a Construction of these hybrids has been described previously (6,33). b Symbols: +, presence of that chromosome in at least 30% of the metaphase cells examined; X, presence of that chromosome in 10 to 30% of the metaphase cells examined.…”

Section: Methodsmentioning

confidence: 99%

“…To determine which human chromosome contains the unique DNA sequences associated with the DNA repair gene, a series of rodent-human hybrids was examined by genomic blot hybridization analysis. These hybrids were derived as described previously (6,33) from eight separate fusion experiments involving six different human diploid fibroblast strains and three different rodent cell lines. Each hybrid contained a full set of hamster or mouse chromosomes but only a partial and varying complement of different combinations of human chromosomes (Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…The chromosomal location of the DNA sequences associated with the human DNA repair gene was determined by gel electrophoresis and blot hybridization analysis of DNA obtained from a series of rodent-human somatic cell hybrids segregating human chromosomes. Construction of these hybrids has been described previously (6,33). Hybrids belonging to series A, L or LT, and W were derived from fusions of human cells with mouse A9 (HPRT-), mouse LTK-, or Chinese hamster line wg3H (HPRT-) cells, respectively.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular cloning and chromosomal localization of DNA sequences associated with a human DNA repair gene.

Rubin¹,

Prideaux²,

Willard³

et al. 1985

Mol. Cell. Biol.

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The genes and gene products involved in the mammalian DNA repair processes have yet to be identified. Toward this end we made use of a number of DNA repair-proficient transformants that were generated after transfection of DNA from repair-proficient human cells into a mutant hamster line that is defective in the initial incision step of the excision repair process. In this report, biochemical evidence is presented that demonstrates that these transformants are repair proficient. In addition, we describe the molecular identification and cloning of unique DNA sequences closely associated with the transfected human DNA repair gene and demonstrate the presence of homologous DNA sequences in human cells and in the repair-proficient DNA transformants. The chromosomal location of these sequences was determined by using a panel of rodent-human somatic cell hybrids. Both unique DNA sequences were found to be on human chromosome 19.

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The T cell receptor β chain genes are located on chromosome 6 in mice and chromosome 7 in humans

Cited by 199 publications

References 44 publications

Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.

Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.

Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells.

Molecular cloning and chromosomal localization of DNA sequences associated with a human DNA repair gene.

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