Skip to main content
NCBI home page
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 Jun;85(11):3933–3937. doi: 10.1073/pnas.85.11.3933

Cloning of the gene encoding the delta subunit of the human T-cell receptor reveals its physical organization within the alpha-subunit locus and its involvement in chromosome translocations in T-cell malignancy.

M Isobe 1, G Russo 1, F G Haluska 1, C M Croce 1
PMCID: PMC280334  PMID: 2836865

Abstract

By taking advantage of "chromosomal walking" techniques, we have obtained clones that encompass the T-cell receptor (TCR) delta-chain gene. We analyzed clones spanning the entire J alpha region extending 115 kilobases 5' of the TCR alpha-chain constant region and have shown that the TCR delta-chain gene is located over 80 kilobases 5' of C alpha. TCR delta-chain gene is rearranged in the gamma/delta-expressing T-cell line Peer and is deleted in alpha/beta-expressing T-cell lines. Sequence analysis of portions of this genomic region demonstrates its identity with previously described cDNA clones corresponding to the C delta and J delta segments. Furthermore, we have analyzed a t(8;14)-(q24;q11) chromosome translocation from a T-cell leukemia and have shown that the J delta segment is rearranged in cells deriving from this tumor and probably directly involved in the translocation. Thus, the newly cloned TCR delta chain is implicated in the genesis of chromosome translocations in T-cell malignancies carrying cytogenetic abnormalities of band 14q11.

Full text

PDF
3933

Images in this article

3935Image
on p.3935
3936Image
on p.3936

Selected References

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

  1. Acuto O., Hussey R. E., Fitzgerald K. A., Protentis J. P., Meuer S. C., Schlossman S. F., Reinherz E. L. The human T cell receptor: appearance in ontogeny and biochemical relationship of alpha and beta subunits on IL-2 dependent clones and T cell tumors. Cell. 1983 Oct;34(3):717–726. doi: 10.1016/0092-8674(83)90528-7. [DOI] [PubMed] [Google Scholar]
  2. Baer R., Forster A., Rabbitts T. H. The mechanism of chromosome 14 inversion in a human T cell lymphoma. Cell. 1987 Jul 3;50(1):97–105. doi: 10.1016/0092-8674(87)90666-0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Brady G., Jantzen H. M., Bernard H. U., Brown R., Schütz G., Hashimoto-Gotoh T. New cosmid vectors developed for eukaryotic DNA cloning. Gene. 1984 Feb;27(2):223–232. doi: 10.1016/0378-1119(84)90143-4. [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., 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]
  8. Croce C. M., Isobe M., Palumbo A., Puck J., Ming J., Tweardy D., Erikson J., Davis M., Rovera G. Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science. 1985 Mar 1;227(4690):1044–1047. doi: 10.1126/science.3919442. [DOI] [PubMed] [Google Scholar]
  9. Denny C. T., Hollis G. F., Hecht F., Morgan R., Link M. P., Smith S. D., Kirsch I. R. Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development. Science. 1986 Oct 10;234(4773):197–200. doi: 10.1126/science.3092355. [DOI] [PubMed] [Google Scholar]
  10. Erikson J., Finger L., Sun L., ar-Rushdi A., Nishikura K., Minowada J., Finan J., Emanuel B. S., Nowell P. C., Croce C. M. Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias. Science. 1986 May 16;232(4752):884–886. doi: 10.1126/science.3486470. [DOI] [PubMed] [Google Scholar]
  11. Erikson J., Williams D. L., Finan J., Nowell P. C., Croce C. M. Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias. Science. 1985 Aug 23;229(4715):784–786. doi: 10.1126/science.3875152. [DOI] [PubMed] [Google Scholar]
  12. Finger L. R., Harvey R. C., Moore R. C., Showe L. C., Croce C. M. A common mechanism of chromosomal translocation in T- and B-cell neoplasia. Science. 1986 Nov 21;234(4779):982–985. doi: 10.1126/science.3490692. [DOI] [PubMed] [Google Scholar]
  13. Grosveld F. G., Dahl H. H., de Boer E., Flavell R. A. Isolation of beta-globin-related genes from a human cosmid library. Gene. 1981 Apr;13(3):227–237. doi: 10.1016/0378-1119(81)90028-7. [DOI] [PubMed] [Google Scholar]
  14. Haluska F. G., Finver S., Tsujimoto Y., Croce C. M. The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. Nature. 1986 Nov 13;324(6093):158–161. doi: 10.1038/324158a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hecht F., Morgan R., Hecht B. K., Smith S. D. Common region on chromosome 14 in T-cell leukemia and lymphoma. Science. 1984 Dec 21;226(4681):1445–1447. doi: 10.1126/science.6438800. [DOI] [PubMed] [Google Scholar]
  17. Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
  18. Hohn B., Murray K. Packaging recombinant DNA molecules into bacteriophage particles in vitro. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3259–3263. doi: 10.1073/pnas.74.8.3259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ish-Horowicz D., Burke J. F. Rapid and efficient cosmid cloning. Nucleic Acids Res. 1981 Jul 10;9(13):2989–2998. doi: 10.1093/nar/9.13.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Isobe M., Erikson J., Emanuel B. S., Nowell P. C., Croce C. M. Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells. Science. 1985 May 3;228(4699):580–582. doi: 10.1126/science.3983641. [DOI] [PubMed] [Google Scholar]
  21. Kagan J., Finan J., Letofsky J., Besa E. C., Nowell P. C., Croce C. M. Alpha-chain locus of the T-cell antigen receptor is involved in the t(10;14) chromosome translocation of T-cell acute lymphocytic leukemia. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4543–4546. doi: 10.1073/pnas.84.13.4543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Koning F., Stingl G., Yokoyama W. M., Yamada H., Maloy W. L., Tschachler E., Shevach E. M., Coligan J. E. Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal Cell lines. Science. 1987 May 15;236(4803):834–837. doi: 10.1126/science.2883729. [DOI] [PubMed] [Google Scholar]
  23. Lew A. M., Pardoll D. M., Maloy W. L., Fowlkes B. J., Kruisbeek A., Cheng S. F., Germain R. N., Bluestone J. A., Schwartz R. H., Coligan J. E. Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes. Science. 1986 Dec 12;234(4782):1401–1405. doi: 10.1126/science.3787252. [DOI] [PubMed] [Google Scholar]
  24. Lindsten T., Fowlkes B. J., Samelson L. E., Davis M. M., Chien Y. H. Transient rearrangements of the T cell antigen receptor alpha locus in early thymocytes. J Exp Med. 1987 Sep 1;166(3):761–775. doi: 10.1084/jem.166.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Mengle-Gaw L., Willard H. F., Smith C. I., Hammarström L., Fischer P., Sherrington P., Lucas G., Thompson P. W., Baer R., Rabbitts T. H. Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32. EMBO J. 1987 Aug;6(8):2273–2280. doi: 10.1002/j.1460-2075.1987.tb02501.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Murre C., Waldmann R. A., Morton C. C., Bongiovanni K. F., Waldmann T. A., Shows T. B., Seidman J. G. Human gamma-chain genes are rearranged in leukaemic T cells and map to the short arm of chromosome 7. Nature. 1985 Aug 8;316(6028):549–552. doi: 10.1038/316549a0. [DOI] [PubMed] [Google Scholar]
  29. Pegoraro L., Palumbo A., Erikson J., Falda M., Giovanazzo B., Emanuel B. S., Rovera G., Nowell P. C., Croce C. M. A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7166–7170. doi: 10.1073/pnas.81.22.7166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Sinha N. D., Biernat J., McManus J., Köster H. Polymer support oligonucleotide synthesis XVIII: use of beta-cyanoethyl-N,N-dialkylamino-/N-morpholino phosphoramidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product. Nucleic Acids Res. 1984 Jun 11;12(11):4539–4557. doi: 10.1093/nar/12.11.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ueshima Y., Rowley J. D., Variakojis D., Winter J., Gordon L. Cytogenetic studies on patients with chronic T cell leukemia/lymphoma. Blood. 1984 May;63(5):1028–1038. [PubMed] [Google Scholar]
  35. Williams D. L., Look A. T., Melvin S. L., Roberson P. K., Dahl G., Flake T., Stass S. New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia. Cell. 1984 Jan;36(1):101–109. doi: 10.1016/0092-8674(84)90078-3. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. Yoshikai Y., Kimura N., Toyonaga B., Mak T. W. Sequences and repertoire of human T cell receptor alpha chain variable region genes in mature T lymphocytes. J Exp Med. 1986 Jul 1;164(1):90–103. doi: 10.1084/jem.164.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yunis J. J. The chromosomal basis of human neoplasia. Science. 1983 Jul 15;221(4607):227–236. doi: 10.1126/science.6336310. [DOI] [PubMed] [Google Scholar]
  40. Zech L., Gahrton G., Hammarström L., Juliusson G., Mellstedt H., Robèrt K. H., Smith C. I. Inversion of chromosome 14 marks human T-cell chronic lymphocytic leukaemia. 1984 Apr 26-May 2Nature. 308(5962):858–860. doi: 10.1038/308858a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES