Skip to main content
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
. 1985 May;82(10):3430–3434. doi: 10.1073/pnas.82.10.3430

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.

Y Yanagi, A Chan, B Chin, M Minden, T W Mak
PMCID: PMC397789  PMID: 3873654

Abstract

We report the isolation and characterization of 19 classes of nonrearranging T cell-specific cDNA clones and two cDNA clones encoding the alpha and beta chains of the T-cell antigen receptor from a human T-cell line, Jurkat. Results indicate that the human alpha-chain gene, like its beta-chain counterpart, undergoes somatic rearrangement in T cells. In addition, it shows sequence homology to its beta-chain counterpart and immunoglobulin, indicating that the human alpha chain is also a member of the immunoglobulin supergene family. Sequence comparison suggests that the alpha 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 alpha- and beta-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.

Full text

PDF
3430

Images in this article

Selected References

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

  1. Acuto O., Fabbi M., Smart J., Poole C. B., Protentis J., Royer H. D., Schlossman S. F., Reinherz E. L. Purification and NH2-terminal amino acid sequencing of the beta subunit of a human T-cell antigen receptor. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3851–3855. doi: 10.1073/pnas.81.12.3851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bothwell A. L., Paskind M., Reth M., Imanishi-Kari T., Rajewsky K., Baltimore D. Somatic variants of murine immunoglobulin lambda light chains. Nature. 1982 Jul 22;298(5872):380–382. doi: 10.1038/298380a0. [DOI] [PubMed] [Google Scholar]
  4. Britten R. J., Graham D. E., Neufeld B. R. Analysis of repeating DNA sequences by reassociation. Methods Enzymol. 1974;29:363–418. doi: 10.1016/0076-6879(74)29033-5. [DOI] [PubMed] [Google Scholar]
  5. Caccia N., Kronenberg M., Saxe D., Haars R., Bruns G. A., Goverman J., Malissen M., Willard H., Yoshikai Y., Simon M. The T cell receptor beta chain genes are located on chromosome 6 in mice and chromosome 7 in humans. Cell. 1984 Jul;37(3):1091–1099. doi: 10.1016/0092-8674(84)90443-4. [DOI] [PubMed] [Google Scholar]
  6. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [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. Clark S. P., Mak T. W. Complete nucleotide sequence of an infectious clone of Friend spleen focus-forming provirus: gp55 is an envelope fusion glycoprotein. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5037–5041. doi: 10.1073/pnas.80.16.5037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark S. P., Yoshikai Y., Taylor S., Siu G., Hood L., Mak T. W. Identification of a diversity segment of human T-cell receptor beta-chain, and comparison with the analogous murine element. 1984 Sep 27-Oct 3Nature. 311(5984):387–389. doi: 10.1038/311387a0. [DOI] [PubMed] [Google Scholar]
  10. Fabbi M., Acuto O., Smart J. E., Reinherz E. L. Homology of Ti alpha-subunit of a T-cell antigen-MHC receptor with immunoglobulin. Nature. 1984 Nov 15;312(5991):269–271. doi: 10.1038/312269a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Kappler J., Kubo R., Haskins K., White J., Marrack P. The mouse T cell receptor: comparison of MHC-restricted receptors on two T cell hybridomas. Cell. 1983 Oct;34(3):727–737. doi: 10.1016/0092-8674(83)90529-9. [DOI] [PubMed] [Google Scholar]
  14. Kurosawa Y., von Boehmer H., Haas W., Sakano H., Trauneker A., Tonegawa S. Identification of D segments of immunoglobulin heavy-chain genes and their rearrangement in T lymphocytes. Nature. 1981 Apr 16;290(5807):565–570. doi: 10.1038/290565a0. [DOI] [PubMed] [Google Scholar]
  15. Mak T. W., Yanagi Y. Genes encoding the human T cell antigen receptor. Immunol Rev. 1984 Oct;81:221–233. doi: 10.1111/j.1600-065x.1984.tb01112.x. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. McIntyre B. W., Allison J. P. The mouse T cell receptor: structural heterogeneity of molecules of normal T cells defined by xenoantiserum. Cell. 1983 Oct;34(3):739–746. doi: 10.1016/0092-8674(83)90530-5. [DOI] [PubMed] [Google Scholar]
  18. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Schneider U., Schwenk H. U., Bornkamm G. Characterization of EBV-genome negative "null" and "T" cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non-Hodgkin lymphoma. Int J Cancer. 1977 May 15;19(5):621–626. doi: 10.1002/ijc.2910190505. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Siu G., Clark S. P., Yoshikai Y., Malissen M., Yanagi Y., Strauss E., Mak T. W., Hood L. The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene. Cell. 1984 Jun;37(2):393–401. doi: 10.1016/0092-8674(84)90369-6. [DOI] [PubMed] [Google Scholar]
  24. Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
  25. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  26. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Toyonaga B., Yanagi Y., Suciu-Foca N., Minden M., Mak T. W. Rearrangements of T-cell receptor gene YT35 in human DNA from thymic leukaemia T-cell lines and functional T-cell clones. 1984 Sep 27-Oct 3Nature. 311(5984):385–387. doi: 10.1038/311385a0. [DOI] [PubMed] [Google Scholar]
  28. Weiss A., Stobo J. D. Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J Exp Med. 1984 Nov 1;160(5):1284–1299. doi: 10.1084/jem.160.5.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Yoshikai Y., Anatoniou D., Clark S. P., Yanagi Y., Sangster R., Van den Elsen P., Terhorst C., Mak T. W. Sequence and expression of transcripts of the human T-cell receptor beta-chain genes. Nature. 1984 Dec 6;312(5994):521–524. doi: 10.1038/312521a0. [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