Skip to main content
PMC 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
. 1985 Jul;82(13):4503–4507. doi: 10.1073/pnas.82.13.4503

Regulation of T-cell receptor gene expression in human T-cell development.

M K Collins, G Tanigawa, A M Kissonerghis, M Ritter, K M Price, S Tonegawa, M J Owen
PMCID: PMC391130  PMID: 3874403

Abstract

A cDNA clone encoding the alpha chain of the human T-cell antigen receptor was isolated by screening a library from the human T-cell line Jurkat with a mouse alpha-chain cDNA clone. This human alpha-chain clone, together with a human antigen receptor beta-chain cDNA clone, was used to determine the stage of T-cell development at which antigen receptor mRNAs first appear. Blot-hybridization analysis of mRNA isolated from a panel of human thymic tumor lines clearly demonstrated that beta-chain transcripts could be detected in all T-lineage cells. However, alpha-chain transcripts were only found in the most phenotypically mature lines, which express the antigen receptor-associated molecule T3. Furthermore, beta-chain transcripts were abundant in RNA prepared from purified T3-negative thymocytes, whereas alpha-chain transcripts were virtually absent. From these results we conclude that alpha-chain expression occurs later in thymic ontogeny than that of the beta chain and propose that it controls surface expression of the antigen receptor-T3 complex.

Full text

PDF

Images in this article

4505Image
on p.4505
4505Image
on p.4505

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. Broder S., Edelson R. L., Lutzner M. A., Nelson D. L., MacDermott R. P., Durm M. E., Goldman C. K., Meade B. D., Waldmann T. A. The Sézary syndrome: a malignant proliferation of helper T cells. J Clin Invest. 1976 Dec;58(6):1297–1306. doi: 10.1172/JCI108585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Chilson O. P., Boylston A. W., Crumpton M. J. Phaseolus vulgaris phytohaemagglutinin (PHA) binds to the human T lymphocyte antigen receptor. EMBO J. 1984 Dec 20;3(13):3239–3245. doi: 10.1002/j.1460-2075.1984.tb02285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Greaves M. F., Rao J., Hariri G., Verbi W., Catovsky D., Kung P., Goldstein G. Phenotypic heterogeneity and cellular origins of T cell malignancies. Leuk Res. 1981;5(4-5):281–299. doi: 10.1016/0145-2126(81)90001-1. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Kavaler J., Davis M. M., Chien Y. Localization of a T-cell receptor diversity-region element. Nature. 1984 Aug 2;310(5976):421–423. doi: 10.1038/310421a0. [DOI] [PubMed] [Google Scholar]
  10. Lamb J. R., Eckels D. D., Lake P., Johnson A. H., Hartzman R. J., Woody J. N. Antigen-specific human T lymphocyte clones: induction, antigen specificity, and MHC restriction of influenza virus-immune clones. J Immunol. 1982 Jan;128(1):233–238. [PubMed] [Google Scholar]
  11. 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]
  12. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Meuer S. C., Acuto O., Hussey R. E., Hodgdon J. C., Fitzgerald K. A., Schlossman S. F., Reinherz E. L. Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor. Nature. 1983 Jun 30;303(5920):808–810. doi: 10.1038/303808a0. [DOI] [PubMed] [Google Scholar]
  15. Raulet D. H., Garman R. D., Saito H., Tonegawa S. Developmental regulation of T-cell receptor gene expression. Nature. 1985 Mar 7;314(6006):103–107. doi: 10.1038/314103a0. [DOI] [PubMed] [Google Scholar]
  16. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Royer H. D., Acuto O., Fabbi M., Tizard R., Ramachandran K., Smart J. E., Reinherz E. L. Genes encoding the Ti beta subunit of the antigen/MHC receptor undergo rearrangement during intrathymic ontogeny prior to surface T3-Ti expression. Cell. 1984 Dec;39(2 Pt 1):261–266. doi: 10.1016/0092-8674(84)90003-5. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. Yoshikai Y., Yanagi Y., Suciu-Foca N., Mak T. W. Presence of T-cell receptor mRNA in functionally distinct T cells and elevation during intrathymic differentiation. Nature. 1984 Aug 9;310(5977):506–508. doi: 10.1038/310506a0. [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