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Human gamma-chain genes are rearranged in leukaemic T cells and map to the short arm of chromosome 7 总被引:1,自引:0,他引:1
C Murre R A Waldmann C C Morton K F Bongiovanni T A Waldmann T B Shows J G Seidman 《Nature》1985,316(6028):549-552
Three gene families that rearrange during the somatic development of T cells have been identified in the murine genome. Two of these gene families (alpha and beta) encode subunits of the antigen-specific T-cell receptor and are also present in the human genome. The third gene family, designated here as the gamma-chain gene family, is rearranged in murine cytolytic T cells but not in most helper T cells. Here we present evidence that the human genome also contains gamma-chain genes that undergo somatic rearrangement in leukaemia-derived T cells. Murine gamma-chain genes appear to be encoded in gene segments that are analogous to the immunoglobulin gene variable, constant and joining segments. There are two closely related constant-region gene segments in the human genome. One of the constant-region genes is deleted in all three T-cell leukaemias that we have studied. The two constant-region gamma-chain genes reside on the short arm of chromosome 7 (7p15); this region is involved in chromosomal rearrangements identified in T cells from individuals with the immunodeficiency syndrome ataxia telangiectasia and observed only rarely in routine cytogenetic analyses of normal individuals. This region is also a secondary site of beta-chain gene hybridization. 相似文献
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Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes 总被引:5,自引:0,他引:5
M B Brenner J McLean H Scheft J Riberdy S L Ang J G Seidman P Devlin M S Krangel 《Nature》1987,325(6106):689-694
The T-cell receptor (TCR) gamma polypeptide is expressed associated with CD3 (T3) on the surface of normal human peripheral blood lymphocytes. These cells function as non-MHC-restricted cytotoxic T lymphocytes (CTL)and thus may play an important role in host immune defence. The TCR gamma polypeptide occurs as a dimer in at least two molecular forms based on the absence or presence of disulphide linkage. These forms use TCR gamma polypeptides with strikingly different peptide backbone sizes. 相似文献
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Identification of a putative second T-cell receptor 总被引:166,自引:0,他引:166
M B Brenner J McLean D P Dialynas J L Strominger J A Smith F L Owen J G Seidman S Ip F Rosen M S Krangel 《Nature》1986,322(6075):145-149
Framework monoclonal antibodies have identified a population of human lymphocytes that express the T3 glycoprotein but not the T-cell receptor (TCR) alpha- and beta-subunits. Chemical crosslinking experiments reveal that these lymphocytes express novel T3-associated polypeptides, one of which appears to be the product of the T gamma gene. The other polypeptide may represent a fourth TCR subunit, designated T delta. 相似文献
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Human T-cell gamma genes contain N segments and have marked junctional variability 总被引:10,自引:0,他引:10
T Quertermous W Strauss C Murre D P Dialynas J L Strominger J G Seidman 《Nature》1986,322(6075):184-187
The gamma-chain genes are encoded by immunoglobulin-like gene segments in germline DNA which rearrange during the somatic development of T cells to form an active gene. The protein produced by these genes has not been identified and the diversity of the proteins that the genes can express has not been determined. We expect that the diversity of expressed gamma-chains is produced by the same three mechanisms that produce diversity of other immunoglobulin-like genes: (1) germline variable (V) and joining (J) region repertoires; (2) somatic mutation; and (3) junctional diversity. To define the contribution of each of these mechanisms to the generation of gamma-chain diversity, several gamma-chain complementary clones and rearranged gamma-chain genes have been characterized. Most of these clones seem to encode a defective gamma-chain, the variable- and constant-region portions being joined such that they would not be translated in the same reading frame. Here we report that the germline J-region diversity of the human T-cell gamma-chain is very limited and that somatic mutation does not contribute to the diversity of the gamma-chains encoded by the cloned segments. However, the junctional diversity of these gamma-chain genes is extensive. We suggest that N sequences (template-independent sequences) have been inserted enzymatically into all of the gamma-chain genes characterized. 相似文献
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Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens 总被引:32,自引:0,他引:32
The mouse major transplantation antigens H-2K, H-2D and H-2L are highly polymorphic cell-surface glycoproteins which may serve as recognition elements in cell-cell interactions. Each antigen possesses a number of alloantigenic determinants defined by antisera of various specificities. Recently, monoclonal antibodies have been produced which redefine and extend our knowledge of these determinants2,3, but structural information has not yet been correlated with the serological definition of the antigens. We have previously reported the molecular cloning of genes for H-2Ld and H-2Dd transplantation antigens from the BALB/c mouse and the expression of these genes in mouse L cells4,5. To localize the serological determinants to discrete regions of the H-2 protein, we have now constructed new H-2 antigen genes by joining together fragments of the H-2Ld and H-2Dd genes. In L cells, these genes direct the synthesis of hybrid H-2 proteins and by using monoclonal antibodies of defined specificities, we have mapped classically defined serological specificities to structurally defined domains of the transplantation antigen protein. We conclude that polymorphic determinants recognized by monoclonal antibodies are located in functionally distinct portions of the protein. 相似文献
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A mutant immunoglobulin light chain is formed by aberrant DNA- and RNA-splicing events 总被引:40,自引:0,他引:40
A mutant immunoglobulin gene has been formed by an abnormal (non V/J) recombination event such that abnormal RNA splicing is required to form a mutant light chain. The structure of the gene suggests that the small palindrome thought to be involved in V/J joining also provides the basis for this abnormal DNA recombination and that the absence of a J segment and RNA splice signal allows an abnormal RNA splicing reaction to occur. 相似文献
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