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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Aug;85(16):6097–6101. doi: 10.1073/pnas.85.16.6097

Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus.

Y Takihara 1, D Tkachuk 1, E Michalopoulos 1, E Champagne 1, J Reimann 1, M Minden 1, T W Mak 1
PMCID: PMC281912  PMID: 3413078

Abstract

In this paper we describe the genomic organization and sequence of the human T-cell receptor delta-chain diversity, joining, and constant genes. There is one delta-chain constant region gene (C delta) located approximately equal to 85 kilobases (kb) upstream of the alpha-chain constant region. The delta-chain constant region consists of four exons, whose organization is very similar to that of the C alpha exons, suggesting that C alpha and C delta may have arisen from a gene duplication event. The first exon encodes most of the extracellular constant domain, the second encodes a hinge-like region, and the third encodes the entire transmembrane segment and intracytoplasmic portion, whereas the last exon contains exclusively 3' untranslated sequences. Three joining segments, J delta 1, J delta 2, and J delta 3, are found approximately equal to 12, approximately equal to 5.7, and approximately equal to 3.4 kb upstream of the first exon of C delta. Two functional diversity gene segments, D delta 1 and D delta 2, which can be productively translated in all three reading frames, are found 1 and 9.6 kb upstream of J delta 1. The presence of two D delta with such potential for diversity may offset the limited repertoire of the J delta and V delta genes. The spacer distribution in the recombinational signals flanking D delta and J delta segments allows recombination with V alpha gene segments; however, examination of delta-chain messages does not indicate that this is the case, suggesting that the delta chain uses unique variable gene segments and raising the question as to the reasons for this phenomenon.

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Selected References

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  1. Band H., Hochstenbach F., McLean J., Hata S., Krangel M. S., Brenner M. B. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science. 1987 Oct 30;238(4827):682–684. doi: 10.1126/science.3672118. [DOI] [PubMed] [Google Scholar]
  2. Bank I., DePinho R. A., Brenner M. B., Cassimeris J., Alt F. W., Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature. 1986 Jul 10;322(6075):179–181. doi: 10.1038/322179a0. [DOI] [PubMed] [Google Scholar]
  3. Bonyhadi M., Weiss A., Tucker P. W., Tigelaar R. E., Allison J. P. Delta is the Cx-gene product in the gamma/delta antigen receptor of dendritic epidermal cells. Nature. 1987 Dec 10;330(6148):574–576. doi: 10.1038/330574a0. [DOI] [PubMed] [Google Scholar]
  4. Born W., Miles C., White J., O'Brien R., Freed J. H., Marrack P., Kappler J., Kubo R. T. Peptide sequences of T-cell receptor delta and gamma chains are identical to predicted X and gamma proteins. Nature. 1987 Dec 10;330(6148):572–574. doi: 10.1038/330572a0. [DOI] [PubMed] [Google Scholar]
  5. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  6. Chien Y. H., Iwashima M., Kaplan K. B., Elliott J. F., Davis M. M. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. 1987 Jun 25-Jul 1Nature. 327(6124):677–682. doi: 10.1038/327677a0. [DOI] [PubMed] [Google Scholar]
  7. Chien Y. H., Iwashima M., Wettstein D. A., Kaplan K. B., Elliott J. F., Born W., Davis M. M. T-cell receptor delta gene rearrangements in early thymocytes. Nature. 1987 Dec 24;330(6150):722–727. doi: 10.1038/330722a0. [DOI] [PubMed] [Google Scholar]
  8. Chien Y., Becker D. M., Lindsten T., Okamura M., Cohen D. I., Davis M. M. A third type of murine T-cell receptor gene. Nature. 1984 Nov 1;312(5989):31–35. doi: 10.1038/312031a0. [DOI] [PubMed] [Google Scholar]
  9. Elliott J. F., Rock E. P., Patten P. A., Davis M. M., Chien Y. H. The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature. 1988 Feb 18;331(6157):627–631. doi: 10.1038/331627a0. [DOI] [PubMed] [Google Scholar]
  10. Gascoigne N. R., Chien Y., Becker D. M., Kavaler J., Davis M. M. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes. Nature. 1984 Aug 2;310(5976):387–391. doi: 10.1038/310387a0. [DOI] [PubMed] [Google Scholar]
  11. Griesser H., Champagne E., Tkachuk D., Takihara Y., Lalande M., Baillie E., Minden M., Mak T. W. The human T cell receptor alpha-delta locus: a physical map of the variable, joining and constant region genes. Eur J Immunol. 1988 Apr;18(4):641–644. doi: 10.1002/eji.1830180424. [DOI] [PubMed] [Google Scholar]
  12. Hata S., Brenner M. B., Krangel M. S. Identification of putative human T cell receptor delta complementary DNA clones. Science. 1987 Oct 30;238(4827):678–682. doi: 10.1126/science.3499667. [DOI] [PubMed] [Google Scholar]
  13. Hayday A. C., Diamond D. J., Tanigawa G., Heilig J. S., Folsom V., Saito H., Tonegawa S. Unusual organization and diversity of T-cell receptor alpha-chain genes. 1985 Aug 29-Sep 4Nature. 316(6031):828–832. doi: 10.1038/316828a0. [DOI] [PubMed] [Google Scholar]
  14. Hayday A. C., Saito H., Gillies S. D., Kranz D. M., Tanigawa G., Eisen H. N., Tonegawa S. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell. 1985 Feb;40(2):259–269. doi: 10.1016/0092-8674(85)90140-0. [DOI] [PubMed] [Google Scholar]
  15. Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [DOI] [PubMed] [Google Scholar]
  16. Iwamoto A., Rupp F., Ohashi P. S., Walker C. L., Pircher H., Joho R., Hengartner H., Mak T. W. T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes. J Exp Med. 1986 May 1;163(5):1203–1212. doi: 10.1084/jem.163.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
  18. Loh E. Y., Lanier L. L., Turck C. W., Littman D. R., Davis M. M., Chien Y. H., Weiss A. Identification and sequence of a fourth human T cell antigen receptor chain. Nature. 1987 Dec 10;330(6148):569–572. doi: 10.1038/330569a0. [DOI] [PubMed] [Google Scholar]
  19. Luria S., Gross G., Horowitz M., Givol D. Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor. EMBO J. 1987 Nov;6(11):3307–3312. doi: 10.1002/j.1460-2075.1987.tb02650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Malissen M., Minard K., Mjolsness S., Kronenberg M., Goverman J., Hunkapiller T., Prystowsky M. B., Yoshikai Y., Fitch F., Mak T. W. Mouse T cell antigen receptor: structure and organization of constant and joining gene segments encoding the beta polypeptide. Cell. 1984 Jul;37(3):1101–1110. doi: 10.1016/0092-8674(84)90444-6. [DOI] [PubMed] [Google Scholar]
  21. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  22. Quertermous T., Murre C., Dialynas D., Duby A. D., Strominger J. L., Waldman T. A., Seidman J. G. Human T-cell gamma chain genes: organization, diversity, and rearrangement. Science. 1986 Jan 17;231(4735):252–255. doi: 10.1126/science.3079918. [DOI] [PubMed] [Google Scholar]
  23. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
  24. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Sim G. K., Yagüe J., Nelson J., Marrack P., Palmer E., Augustin A., Kappler J. Primary structure of human T-cell receptor alpha-chain. Nature. 1984 Dec 20;312(5996):771–775. doi: 10.1038/312771a0. [DOI] [PubMed] [Google Scholar]
  27. Takihara Y., Champagne E., Griesser H., Kimura N., Tkachuk D., Reimann J., Okada A., Alt F. W., Chess L., Minden M. Sequence and organization of the human T cell delta chain gene. Eur J Immunol. 1988 Feb;18(2):283–287. doi: 10.1002/eji.1830180216. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Toyonaga B., Yoshikai Y., Vadasz V., Chin B., Mak T. W. Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8624–8628. doi: 10.1073/pnas.82.24.8624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Winoto A., Mjolsness S., Hood L. Genomic organization of the genes encoding mouse T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):832–836. doi: 10.1038/316832a0. [DOI] [PubMed] [Google Scholar]
  31. Yanagi Y., Chan A., Chin B., Minden M., Mak T. W. 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. Proc Natl Acad Sci U S A. 1985 May;82(10):3430–3434. doi: 10.1073/pnas.82.10.3430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yanagi Y., Yoshikai Y., Leggett K., Clark S. P., Aleksander I., Mak T. W. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature. 1984 Mar 8;308(5955):145–149. doi: 10.1038/308145a0. [DOI] [PubMed] [Google Scholar]
  33. Yoshikai Y., Clark S. P., Taylor S., Sohn U., Wilson B. I., Minden M. D., Mak T. W. Organization and sequences of the variable, joining and constant region genes of the human T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):837–840. doi: 10.1038/316837a0. [DOI] [PubMed] [Google Scholar]

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