Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Oct 1;174(4):775–783. doi: 10.1084/jem.174.4.775

Surface expression of a T cell receptor beta (TCR-beta) chain in the absence of TCR-alpha, -delta, and -gamma proteins

PMCID: PMC2118962  PMID: 1717631

Abstract

The antigen receptor expressed by mature T cells has been described as a disulfide-linked alpha/beta or gamma/delta heterodimer noncovalently associated with CD3, a complex of transmembrane proteins that communicates signals from the T cell receptor (TCR) to the cell interior. Studies suggest that all component chains must assemble intracellularly before surface expression can be achieved. We described, however, a CD4+/CD8+ transformed murine thymocyte, KKF, that expresses surface TCR-beta chains in the absence of gamma, delta, and alpha proteins; these beta chains are only weakly associated with CD3- epsilon and CD3-zeta. Furthermore, KKF responds differently to stimulation through TCR-beta and CD3-epsilon, a functional dissociation that has been ascribed to a CD4+/CD8+ subpopulation of normal thymocytes. KKF's unique TCR structure may offer an explanation for the functional anomalies observed.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Becker M. L., Near R., Mudgett-Hunter M., Margolies M. N., Kubo R. T., Kaye J., Hedrick S. M. Expression of a hybrid immunoglobulin-T cell receptor protein in transgenic mice. Cell. 1989 Sep 8;58(5):911–921. doi: 10.1016/0092-8674(89)90943-4. [DOI] [PubMed] [Google Scholar]
  2. Berg L. J., Fazekas de St Groth B., Pullen A. M., Davis M. M. Phenotypic differences between alpha beta versus beta T-cell receptor transgenic mice undergoing negative selection. Nature. 1989 Aug 17;340(6234):559–562. doi: 10.1038/340559a0. [DOI] [PubMed] [Google Scholar]
  3. Blackman M., Kappler J., Marrack P. The role of the T cell receptor in positive and negative selection of developing T cells. Science. 1990 Jun 15;248(4961):1335–1341. doi: 10.1126/science.1972592. [DOI] [PubMed] [Google Scholar]
  4. Bonifacino J. S., Suzuki C. K., Lippincott-Schwartz J., Weissman A. M., Klausner R. D. Pre-Golgi degradation of newly synthesized T-cell antigen receptor chains: intrinsic sensitivity and the role of subunit assembly. J Cell Biol. 1989 Jul;109(1):73–83. doi: 10.1083/jcb.109.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brenner M. B., Trowbridge I. S., Strominger J. L. Cross-linking of human T cell receptor proteins: association between the T cell idiotype beta subunit and the T3 glycoprotein heavy subunit. Cell. 1985 Jan;40(1):183–190. doi: 10.1016/0092-8674(85)90321-6. [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. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Dembić Z., Bannwarth W., Taylor B. A., Steinmetz M. The gene encoding the T-cell receptor alpha-chain maps close to the Np-2 locus on mouse chromosome 14. Nature. 1985 Mar 21;314(6008):271–273. doi: 10.1038/314271a0. [DOI] [PubMed] [Google Scholar]
  12. Finkel T. H., Cambier J. C., Kubo R. T., Born W. K., Marrack P., Kappler J. W. The thymus has two functionally distinct populations of immature alpha beta + T cells: one population is deleted by ligation of alpha beta TCR. Cell. 1989 Sep 22;58(6):1047–1054. doi: 10.1016/0092-8674(89)90503-5. [DOI] [PubMed] [Google Scholar]
  13. Finkel T. H., Marrack P., Kappler J. W., Kubo R. T., Cambier J. C. Alpha beta T cell receptor and CD3 transduce different signals in immature T cells. Implications for selection and tolerance. J Immunol. 1989 May 1;142(9):3006–3012. [PubMed] [Google Scholar]
  14. Finkel T. H., McDuffie M., Kappler J. W., Marrack P., Cambier J. C. Both immature and mature T cells mobilize Ca2+ in response to antigen receptor crosslinking. Nature. 1987 Nov 12;330(6144):179–181. doi: 10.1038/330179a0. [DOI] [PubMed] [Google Scholar]
  15. Frank S. J., Niklinska B. B., Orloff D. G., Merćep M., Ashwell J. D., Klausner R. D. Structural mutations of the T cell receptor zeta chain and its role in T cell activation. Science. 1990 Jul 13;249(4965):174–177. doi: 10.1126/science.2371564. [DOI] [PubMed] [Google Scholar]
  16. Geisler C., Schøller J., Wahi M. A., Rubin B., Weiss A. Association of the human CD3-zeta chain with the alpha beta-T cell receptor/CD3 complex. Clues from a T cell variant with a mutated T cell receptor-alpha chain. J Immunol. 1990 Sep 15;145(6):1761–1767. [PubMed] [Google Scholar]
  17. Goverman J., Gomez S. M., Segesman K. D., Hunkapiller T., Laug W. E., Hood L. Chimeric immunoglobulin-T cell receptor proteins form functional receptors: implications for T cell receptor complex formation and activation. Cell. 1990 Mar 23;60(6):929–939. doi: 10.1016/0092-8674(90)90341-b. [DOI] [PubMed] [Google Scholar]
  18. Hashimoto Y., Blank K. J. T cell receptor genes and T cell development in virus-transformed early T cell lines. J Immunol. 1990 Feb 15;144(4):1518–1525. [PubMed] [Google Scholar]
  19. Hashimoto Y., Maxam A. M., Greene M. I. T-cell antigen-receptor genes in autoimmune mice. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7865–7869. doi: 10.1073/pnas.83.20.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Havran W. L., Poenie M., Kimura J., Tsien R., Weiss A., Allison J. P. Expression and function of the CD3-antigen receptor on murine CD4+8+ thymocytes. Nature. 1987 Nov 12;330(6144):170–173. doi: 10.1038/330170a0. [DOI] [PubMed] [Google Scholar]
  21. Heber-Katz E., Schwartz R. H., Matis L. A., Hannum C., Fairwell T., Appella E., Hansburg D. Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation. J Exp Med. 1982 Apr 1;155(4):1086–1099. doi: 10.1084/jem.155.4.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hochstenbach F., Brenner M. B. T-cell receptor delta-chain can substitute for alpha to form a beta delta heterodimer. Nature. 1989 Aug 17;340(6234):562–565. doi: 10.1038/340562a0. [DOI] [PubMed] [Google Scholar]
  23. Itohara S., Nakanishi N., Kanagawa O., Kubo R., Tonegawa S. Monoclonal antibodies specific to native murine T-cell receptor gamma delta: analysis of gamma delta T cells during thymic ontogeny and in peripheral lymphoid organs. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5094–5098. doi: 10.1073/pnas.86.13.5094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Kisielow P., Teh H. S., Blüthmann H., von Boehmer H. Positive selection of antigen-specific T cells in thymus by restricting MHC molecules. Nature. 1988 Oct 20;335(6192):730–733. doi: 10.1038/335730a0. [DOI] [PubMed] [Google Scholar]
  26. Korman A. J., Maruyama J., Raulet D. H. Rearrangement by inversion of a T-cell receptor delta variable region gene located 3' of the delta constant region gene. Proc Natl Acad Sci U S A. 1989 Jan;86(1):267–271. doi: 10.1073/pnas.86.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  28. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  29. Lippincott-Schwartz J., Bonifacino J. S., Yuan L. C., Klausner R. D. Degradation from the endoplasmic reticulum: disposing of newly synthesized proteins. Cell. 1988 Jul 15;54(2):209–220. doi: 10.1016/0092-8674(88)90553-3. [DOI] [PubMed] [Google Scholar]
  30. Loh E. Y., Elliott J. F., Cwirla S., Lanier L. L., Davis M. M. Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science. 1989 Jan 13;243(4888):217–220. doi: 10.1126/science.2463672. [DOI] [PubMed] [Google Scholar]
  31. Manolios N., Bonifacino J. S., Klausner R. D. Transmembrane helical interactions and the assembly of the T cell receptor complex. Science. 1990 Jul 20;249(4966):274–277. doi: 10.1126/science.2142801. [DOI] [PubMed] [Google Scholar]
  32. Marusić-Galesić S., Pardoll D. M., Saito T., Leo O., Fowlkes B. J., Coligan J., Germain R. N., Schwartz R. H., Kruisbeek A. M. Activation properties of T cell receptor-gamma delta hybridomas expressing diversity in both gamma- and delta-chains. J Immunol. 1988 Jan 15;140(2):411–418. [PubMed] [Google Scholar]
  33. Saito T., Weiss A., Gunter K. C., Shevach E. M., Germain R. N. Cell surface T3 expression requires the presence of both alpha- and beta-chains of the T cell receptor. J Immunol. 1987 Jul 15;139(2):625–628. [PubMed] [Google Scholar]
  34. Samelson L. E., Harford J. B., Klausner R. D. Identification of the components of the murine T cell antigen receptor complex. Cell. 1985 Nov;43(1):223–231. doi: 10.1016/0092-8674(85)90027-3. [DOI] [PubMed] [Google Scholar]
  35. Spencer J. S., Kubo R. T. Mixed isotype class II antigen expression. A novel class II molecule is expressed on a murine B cell lymphoma. J Exp Med. 1989 Mar 1;169(3):625–640. doi: 10.1084/jem.169.3.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Takeshita S., Toda M., Yamagishi H. Excision products of the T cell receptor gene support a progressive rearrangement model of the alpha/delta locus. EMBO J. 1989 Nov;8(11):3261–3270. doi: 10.1002/j.1460-2075.1989.tb08486.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Teh H. S., Kisielow P., Scott B., Kishi H., Uematsu Y., Blüthmann H., von Boehmer H. Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells. Nature. 1988 Sep 15;335(6187):229–233. doi: 10.1038/335229a0. [DOI] [PubMed] [Google Scholar]
  38. Thomas P. S. Hybridization of denatured RNA transferred or dotted nitrocellulose paper. Methods Enzymol. 1983;100:255–266. doi: 10.1016/0076-6879(83)00060-9. [DOI] [PubMed] [Google Scholar]
  39. Weiss A., Dazin P. F., Shields R., Fu S. M., Lanier L. L. Functional competency of T cell antigen receptors in human thymus. J Immunol. 1987 Nov 15;139(10):3245–3250. [PubMed] [Google Scholar]
  40. Zaller D. M., Osman G., Kanagawa O., Hood L. Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor V beta-specific antibodies. J Exp Med. 1990 Jun 1;171(6):1943–1955. doi: 10.1084/jem.171.6.1943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. von Boehmer H., Bonneville M., Ishida I., Ryser S., Lincoln G., Smith R. T., Kishi H., Scott B., Kisielow P., Tonegawa S. Early expression of a T-cell receptor beta-chain transgene suppresses rearrangement of the V gamma 4 gene segment. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9729–9732. doi: 10.1073/pnas.85.24.9729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. von Boehmer H., Kisielow P. Self-nonself discrimination by T cells. Science. 1990 Jun 15;248(4961):1369–1373. doi: 10.1126/science.1972594. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES