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. 1991 Dec 1;174(6):1537–1547. doi: 10.1084/jem.174.6.1537

The genomic structure of human V beta 6 T cell antigen receptor genes [published erratum appears in J Exp Med 1992 Feb 1;175(2):617]

PMCID: PMC2119020  PMID: 1660526

Abstract

Six genomic clones were characterized containing members of the human V beta 6 subfamily of T cell antigen receptor genes. There were four major findings. (a) New V beta genes were discovered, including V beta 6.10, V beta 13.4, V beta 13.5, and V beta 5.5. (b) Members of the V beta 13, V beta 6, and V beta 5 subfamilies cluster together in the V beta locus and may have evolved through multiple duplication events of an ancestral cassette containing V beta 13-V beta 6-V beta 5 genes. These V beta subfamilies are used by an estimated one-third of T cells in humans and probably represent a highly useful component of the V beta repertoire. (c) The promoters of V beta 13, V beta 6, and V beta 5 genes contain conserved decamer motifs, but discrete differences were observed between promoters of different V beta subfamilies, raising the question of different transcriptional control depending on V beta subfamily usage. (d) The new V beta 6.10 gene is probably a pseudogene, which may have been inactivated due to retrotransposition of Alu elements into its promoter region, a mutation affecting a highly conserved cysteine residue or mutations of the 3' recombinase signal sequence.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson S. J., Chou H. S., Loh D. Y. A conserved sequence in the T-cell receptor beta-chain promoter region. Proc Natl Acad Sci U S A. 1988 May;85(10):3551–3554. doi: 10.1073/pnas.85.10.3551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Canaani E., Dreazen O., Klar A., Rechavi G., Ram D., Cohen J. B., Givol D. Activation of the c-mos oncogene in a mouse plasmacytoma by insertion of an endogenous intracisternal A-particle genome. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7118–7122. doi: 10.1073/pnas.80.23.7118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Concannon P., Pickering L. A., Kung P., Hood L. Diversity and structure of human T-cell receptor beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6598–6602. doi: 10.1073/pnas.83.17.6598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  6. Duby A. D., Seidman J. G. Abnormal recombination products result from aberrant DNA rearrangement of the human T-cell antigen receptor beta-chain gene. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4890–4894. doi: 10.1073/pnas.83.13.4890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferradini L., Roman-Roman S., Azocar J., Michalaki H., Triebel F., Hercend T. Studies on the human T cell receptor alpha/beta variable region genes. II. Identification of four additional V beta subfamilies. Eur J Immunol. 1991 Apr;21(4):935–942. doi: 10.1002/eji.1830210412. [DOI] [PubMed] [Google Scholar]
  8. Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
  9. Ghosh D. A relational database of transcription factors. Nucleic Acids Res. 1990 Apr 11;18(7):1749–1756. doi: 10.1093/nar/18.7.1749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gottschalk L. R., Leiden J. M. Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes. Mol Cell Biol. 1990 Oct;10(10):5486–5495. doi: 10.1128/mcb.10.10.5486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hamada H., Petrino M. G., Kakunaga T., Seidman M., Stollar B. D. Characterization of genomic poly(dT-dG).poly(dC-dA) sequences: structure, organization, and conformation. Mol Cell Biol. 1984 Dec;4(12):2610–2621. doi: 10.1128/mcb.4.12.2610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hamada H., Seidman M., Howard B. H., Gorman C. M. Enhanced gene expression by the poly(dT-dG).poly(dC-dA) sequence. Mol Cell Biol. 1984 Dec;4(12):2622–2630. doi: 10.1128/mcb.4.12.2622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hawley R. G., Shulman M. J., Murialdo H., Gibson D. M., Hozumi N. Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7425–7429. doi: 10.1073/pnas.79.23.7425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hinkkanen A. E., Steimle V., Schlesier M., Peter H. H., Epplen J. T. The antigen receptor of an autoreactive T-cell clone from human rheumatic synovia. Immunogenetics. 1989;29(2):131–133. doi: 10.1007/BF00395864. [DOI] [PubMed] [Google Scholar]
  15. Ho I. C., Yang L. H., Morle G., Leiden J. M. A T-cell-specific transcriptional enhancer element 3' of C alpha in the human T-cell receptor alpha locus. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6714–6718. doi: 10.1073/pnas.86.17.6714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jelinek W. R., Schmid C. W. Repetitive sequences in eukaryotic DNA and their expression. Annu Rev Biochem. 1982;51:813–844. doi: 10.1146/annurev.bi.51.070182.004121. [DOI] [PubMed] [Google Scholar]
  17. Kazazian H. H., Jr, Wong C., Youssoufian H., Scott A. F., Phillips D. G., Antonarakis S. E. Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature. 1988 Mar 10;332(6160):164–166. doi: 10.1038/332164a0. [DOI] [PubMed] [Google Scholar]
  18. Kimura N., Toyonaga B., Yoshikai Y., Du R. P., Mak T. W. Sequences and repertoire of the human T cell receptor alpha and beta chain variable region genes in thymocytes. Eur J Immunol. 1987 Mar;17(3):375–383. doi: 10.1002/eji.1830170312. [DOI] [PubMed] [Google Scholar]
  19. Kimura N., Toyonaga B., Yoshikai Y., Triebel F., Debre P., Minden M. D., Mak T. W. Sequences and diversity of human T cell receptor beta chain variable region genes. J Exp Med. 1986 Sep 1;164(3):739–750. doi: 10.1084/jem.164.3.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Krimpenfort P., de Jong R., Uematsu Y., Dembic Z., Ryser S., von Boehmer H., Steinmetz M., Berns A. Transcription of T cell receptor beta-chain genes is controlled by a downstream regulatory element. EMBO J. 1988 Mar;7(3):745–750. doi: 10.1002/j.1460-2075.1988.tb02871.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lai E., Concannon P., Hood L. Conserved organization of the human and murine T-cell receptor beta-gene families. Nature. 1988 Feb 11;331(6156):543–546. doi: 10.1038/331543a0. [DOI] [PubMed] [Google Scholar]
  22. Lee M. G., Loomis C., Cowan N. J. Sequence of an expressed human beta-tubulin gene containing ten Alu family members. Nucleic Acids Res. 1984 Jul 25;12(14):5823–5836. doi: 10.1093/nar/12.14.5823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  24. Leiden J. M., Dialynas D. P., Duby A. D., Murre C., Seidman J., Strominger J. L. Rearrangement and expression of T-cell antigen receptor genes in human T-lymphocyte tumor lines and normal human T-cell clones: evidence for allelic exclusion of Ti beta gene expression and preferential use of a J beta 2 gene segment. Mol Cell Biol. 1986 Sep;6(9):3207–3214. doi: 10.1128/mcb.6.9.3207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Leiden J. M., Strominger J. L. Generation of diversity of the beta chain of the human T-lymphocyte receptor for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4456–4460. doi: 10.1073/pnas.83.12.4456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Li Y., Szabo P., Robinson M. A., Dong B., Posnett D. N. Allelic variations in the human T cell receptor V beta 6.7 gene products. J Exp Med. 1990 Jan 1;171(1):221–230. doi: 10.1084/jem.171.1.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lin C. S., Goldthwait D. A., Samols D. Identification of Alu transposition in human lung carcinoma cells. Cell. 1988 Jul 15;54(2):153–159. doi: 10.1016/0092-8674(88)90547-8. [DOI] [PubMed] [Google Scholar]
  28. Maecker H. T., Levy R. Prevalence of antigen receptor variants in human T cell lines and tumors. J Immunol. 1989 Feb 15;142(4):1395–1404. [PubMed] [Google Scholar]
  29. Mager D. L., Goodchild N. L. Homologous recombination between the LTRs of a human retrovirus-like element causes a 5-kb deletion in two siblings. Am J Hum Genet. 1989 Dec;45(6):848–854. [PMC free article] [PubMed] [Google Scholar]
  30. Man Y. M., Delius H., Leader D. P. Molecular analysis of elements inserted into mouse gamma-actin processed pseudogenes. Nucleic Acids Res. 1987 Apr 24;15(8):3291–3304. doi: 10.1093/nar/15.8.3291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Montminy M. R., Bilezikjian L. M. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature. 1987 Jul 9;328(6126):175–178. doi: 10.1038/328175a0. [DOI] [PubMed] [Google Scholar]
  32. Montminy M. R., Sevarino K. A., Wagner J. A., Mandel G., Goodman R. H. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682–6686. doi: 10.1073/pnas.83.18.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nordheim A., Rich A. Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences. Nature. 1983 Jun 23;303(5919):674–679. doi: 10.1038/303674a0. [DOI] [PubMed] [Google Scholar]
  34. Nordheim A., Rich A. The sequence (dC-dA)n X (dG-dT)n forms left-handed Z-DNA in negatively supercoiled plasmids. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1821–1825. doi: 10.1073/pnas.80.7.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Posnett D. N. Allelic variations of human TCR V gene products. Immunol Today. 1990 Oct;11(10):368–373. doi: 10.1016/0167-5699(90)90143-w. [DOI] [PubMed] [Google Scholar]
  36. Posnett D. N., Gottlieb A., Bussel J. B., Friedman S. M., Chiorazzi N., Li Y., Szabo P., Farid N. R., Robinson M. A. T cell antigen receptors in autoimmunity. J Immunol. 1988 Sep 15;141(6):1963–1969. [PubMed] [Google Scholar]
  37. Posnett D. N., Wang C. Y., Friedman S. M. Inherited polymorphism of the human T-cell antigen receptor detected by a monoclonal antibody. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7888–7892. doi: 10.1073/pnas.83.20.7888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Redondo J. M., Hata S., Brocklehurst C., Krangel M. S. A T cell-specific transcriptional enhancer within the human T cell receptor delta locus. Science. 1990 Mar 9;247(4947):1225–1229. doi: 10.1126/science.2156339. [DOI] [PubMed] [Google Scholar]
  39. Robinson M. A. Allelic sequence variations in the hypervariable region of a T-cell receptor beta chain: correlation with restriction fragment length polymorphism in human families and populations. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9422–9426. doi: 10.1073/pnas.86.23.9422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Robinson M. A. The human T cell receptor beta-chain gene complex contains at least 57 variable gene segments. Identification of six V beta genes in four new gene families. J Immunol. 1991 Jun 15;146(12):4392–4397. [PubMed] [Google Scholar]
  41. Royer H. D., Reinherz E. L. Multiple nuclear proteins bind upstream sequences in the promotor region of a T-cell receptor beta-chain variable-region gene: evidence for tissue specificity. Proc Natl Acad Sci U S A. 1987 Jan;84(1):232–236. doi: 10.1073/pnas.84.1.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
  43. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schiffer M., Wu T. T., Kabat E. A. Subgroups of variable region genes of beta chains of T-cell receptors for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4461–4463. doi: 10.1073/pnas.83.12.4461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Siu G., Strauss E. C., Lai E., Hood L. E. Analysis of a human V beta gene subfamily. J Exp Med. 1986 Nov 1;164(5):1600–1614. doi: 10.1084/jem.164.5.1600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sobel E., Martinez H. M. A multiple sequence alignment program. Nucleic Acids Res. 1986 Jan 10;14(1):363–374. doi: 10.1093/nar/14.1.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Tillinghast J. P., Behlke M. A., Loh D. Y. Structure and diversity of the human T-cell receptor beta-chain variable region genes. Science. 1986 Aug 22;233(4766):879–883. doi: 10.1126/science.3755549. [DOI] [PubMed] [Google Scholar]
  48. Toyonaga B., Mak T. W. Genes of the T-cell antigen receptor in normal and malignant T cells. Annu Rev Immunol. 1987;5:585–620. doi: 10.1146/annurev.iy.05.040187.003101. [DOI] [PubMed] [Google Scholar]
  49. Ullu E., Tschudi C. Alu sequences are processed 7SL RNA genes. Nature. 1984 Nov 8;312(5990):171–172. doi: 10.1038/312171a0. [DOI] [PubMed] [Google Scholar]
  50. Vogt P. K., Bos T. J. The oncogene jun and nuclear signalling. Trends Biochem Sci. 1989 May;14(5):172–175. doi: 10.1016/0968-0004(89)90268-5. [DOI] [PubMed] [Google Scholar]
  51. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  52. Weiner A. M., Deininger P. L., Efstratiadis A. Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu Rev Biochem. 1986;55:631–661. doi: 10.1146/annurev.bi.55.070186.003215. [DOI] [PubMed] [Google Scholar]
  53. Wilson R. K., Lai E., Concannon P., Barth R. K., Hood L. E. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev. 1988 Jan;101:149–172. doi: 10.1111/j.1600-065x.1988.tb00736.x. [DOI] [PubMed] [Google Scholar]
  54. Winoto A., Baltimore D. A novel, inducible and T cell-specific enhancer located at the 3' end of the T cell receptor alpha locus. EMBO J. 1989 Mar;8(3):729–733. doi: 10.1002/j.1460-2075.1989.tb03432.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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