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. 1992 Jul;11(7):2735–2745. doi: 10.1002/j.1460-2075.1992.tb05339.x

T cell receptor (TCR) beta chain homodimers on the surface of immature but not mature alpha, gamma, delta chain deficient T cell lines.

M Groettrup 1, A Baron 1, G Griffiths 1, R Palacios 1, H von Boehmer 1
PMCID: PMC556749  PMID: 1385777

Abstract

Transfected T cell receptor (TCR) beta chain genes are expressed as homodimers on the surface of immature (Sci/ET27F) but not on mature (58 alpha-beta-) T cell lines which lack TCR alpha, gamma and delta chains. The homodimer on Sci/ET27F cells is tightly bound to CD3 delta and CD3 epsilon while the association with CD3 gamma and CD3 zeta proteins is rather weak. Crosslinking of the TCR beta homodimers resulted in a strong and rapid calcium flux. In 58 alpha-beta- T cells the beta TCR chain could be easily visualized intracellularly but was not transported to the cell surface. The Scid cell lines considerably facilitate the molecular analysis of early differentiation events in the thymus which are likely to be regulated by the beta TCR homodimer.

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Selected References

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

  1. Alarcon B., Berkhout B., Breitmeyer J., Terhorst C. Assembly of the human T cell receptor-CD3 complex takes place in the endoplasmic reticulum and involves intermediary complexes between the CD3-gamma.delta.epsilon core and single T cell receptor alpha or beta chains. J Biol Chem. 1988 Feb 25;263(6):2953–2961. [PubMed] [Google Scholar]
  2. Ashwell J. D., Klusner R. D. Genetic and mutational analysis of the T-cell antigen receptor. Annu Rev Immunol. 1990;8:139–167. doi: 10.1146/annurev.iy.08.040190.001035. [DOI] [PubMed] [Google Scholar]
  3. Bonifacino J. S., Cosson P., Shah N., Klausner R. D. Role of potentially charged transmembrane residues in targeting proteins for retention and degradation within the endoplasmic reticulum. EMBO J. 1991 Oct;10(10):2783–2793. doi: 10.1002/j.1460-2075.1991.tb07827.x. [DOI] [PMC free article] [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. Bonneville M., Janeway C. A., Jr, Ito K., Haser W., Ishida I., Nakanishi N., Tonegawa S. Intestinal intraepithelial lymphocytes are a distinct set of gamma delta T cells. Nature. 1988 Dec 1;336(6198):479–481. doi: 10.1038/336479a0. [DOI] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Dennert G., Hyman R., Lesley J., Trowbridge I. S. Effects of cytotoxic monoclonal antibody specific for T200 glycoprotein on functional lymphoid cell populations. Cell Immunol. 1980 Aug 1;53(2):350–364. doi: 10.1016/0008-8749(80)90335-4. [DOI] [PubMed] [Google Scholar]
  8. Duplay P., Lancki D., Allison J. P. Distribution and ontogeny of CD2 expression by murine T cells. J Immunol. 1989 May 1;142(9):2998–3005. [PubMed] [Google Scholar]
  9. Haars R., Kronenberg M., Gallatin W. M., Weissman I. L., Owen F. L., Hood L. Rearrangement and expression of T cell antigen receptor and gamma genes during thymic development. J Exp Med. 1986 Jul 1;164(1):1–24. doi: 10.1084/jem.164.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. Kincade P. W., Lee G., Watanabe T., Sun L., Scheid M. P. Antigens displayed on murine B lymphocyte precursors. J Immunol. 1981 Dec;127(6):2262–2268. [PubMed] [Google Scholar]
  14. Kishi H., Borgulya P., Scott B., Karjalainen K., Traunecker A., Kaufman J., von Boehmer H. Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells. EMBO J. 1991 Jan;10(1):93–100. doi: 10.1002/j.1460-2075.1991.tb07924.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kitamura D., Roes J., Kühn R., Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991 Apr 4;350(6317):423–426. doi: 10.1038/350423a0. [DOI] [PubMed] [Google Scholar]
  16. Krimpenfort P., Ossendorp F., Borst J., Melief C., Berns A. T cell depletion in transgenic mice carrying a mutant gene for TCR-beta. Nature. 1989 Oct 26;341(6244):742–746. doi: 10.1038/341742a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Kudo A., Melchers F. A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. EMBO J. 1987 Aug;6(8):2267–2272. doi: 10.1002/j.1460-2075.1987.tb02500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lanier L. L., Yu G., Phillips J. H. Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Nature. 1989 Dec 14;342(6251):803–805. doi: 10.1038/342803a0. [DOI] [PubMed] [Google Scholar]
  20. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Letourneur F., Malissen B. Derivation of a T cell hybridoma variant deprived of functional T cell receptor alpha and beta chain transcripts reveals a nonfunctional alpha-mRNA of BW5147 origin. Eur J Immunol. 1989 Dec;19(12):2269–2274. doi: 10.1002/eji.1830191214. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Malek T. R., Robb R. J., Shevach E. M. Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5694–5698. doi: 10.1073/pnas.80.18.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Manolios N., Letourneur F., Bonifacino J. S., Klausner R. D. Pairwise, cooperative and inhibitory interactions describe the assembly and probable structure of the T-cell antigen receptor. EMBO J. 1991 Jul;10(7):1643–1651. doi: 10.1002/j.1460-2075.1991.tb07687.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Manz J., Denis K., Witte O., Brinster R., Storb U. Feedback inhibition of immunoglobulin gene rearrangement by membrane mu, but not by secreted mu heavy chains. J Exp Med. 1988 Oct 1;168(4):1363–1381. doi: 10.1084/jem.168.4.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nussenzweig M. C., Shaw A. C., Sinn E., Danner D. B., Holmes K. L., Morse H. C., 3rd, Leder P. Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu. Science. 1987 May 15;236(4803):816–819. doi: 10.1126/science.3107126. [DOI] [PubMed] [Google Scholar]
  27. Palacios R., Studer S., Samaridis J., Pelkonen J. Thymic epithelial cells induce in vitro differentiation of PRO-T lymphocyte clones into TCR alpha,beta/T3+ and TCR gamma,delta/T3+ cells. EMBO J. 1989 Dec 20;8(13):4053–4063. doi: 10.1002/j.1460-2075.1989.tb08589.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pillai S., Baltimore D. Formation of disulphide-linked mu 2 omega 2 tetramers in pre-B cells by the 18K omega-immunoglobulin light chain. Nature. 1987 Sep 10;329(6135):172–174. doi: 10.1038/329172a0. [DOI] [PubMed] [Google Scholar]
  29. Pillai S., Baltimore D. The omega and iota surrogate immunoglobulin light chains. Curr Top Microbiol Immunol. 1988;137:136–139. doi: 10.1007/978-3-642-50059-6_20. [DOI] [PubMed] [Google Scholar]
  30. Punt J. A., Kubo R. T., Saito T., Finkel T. H., Kathiresan S., Blank K. J., Hashimoto Y. Surface expression of a T cell receptor beta (TCR-beta) chain in the absence of TCR-alpha, -delta, and -gamma proteins. J Exp Med. 1991 Oct 1;174(4):775–783. doi: 10.1084/jem.174.4.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pérez-Aciego P., Alarcón B., Arnaiz-Villena A., Terhorst C., Timón M., Segurado O. G., Regueiro J. R. Expression and function of a variant T cell receptor complex lacking CD3-gamma. J Exp Med. 1991 Aug 1;174(2):319–326. doi: 10.1084/jem.174.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Reth M., Petrac E., Wiese P., Lobel L., Alt F. W. Activation of V kappa gene rearrangement in pre-B cells follows the expression of membrane-bound immunoglobulin heavy chains. EMBO J. 1987 Nov;6(11):3299–3305. doi: 10.1002/j.1460-2075.1987.tb02649.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sakaguchi N., Melchers F. Lambda 5, a new light-chain-related locus selectively expressed in pre-B lymphocytes. Nature. 1986 Dec 11;324(6097):579–582. doi: 10.1038/324579a0. [DOI] [PubMed] [Google Scholar]
  35. Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986 Sep 26;46(7):963–972. doi: 10.1016/0092-8674(86)90695-1. [DOI] [PubMed] [Google Scholar]
  36. Sen J., Arceci R. J., Jones W., Burakoff S. J. Expression and ontogeny of murine CD2. Eur J Immunol. 1989 Jul;19(7):1297–1302. doi: 10.1002/eji.1830190722. [DOI] [PubMed] [Google Scholar]
  37. Shores E. W., Sharrow S. O., Uppenkamp I., Singer A. T cell receptor-negative thymocytes from SCID mice can be induced to enter the CD4/CD8 differentiation pathway. Eur J Immunol. 1990 Jan;20(1):69–77. doi: 10.1002/eji.1830200111. [DOI] [PubMed] [Google Scholar]
  38. Snodgrass H. R., Kisielow P., Kiefer M., Steinmetz M., von Boehmer H. Ontogeny of the T-cell antigen receptor within the thymus. Nature. 1985 Feb 14;313(6003):592–595. doi: 10.1038/313592a0. [DOI] [PubMed] [Google Scholar]
  39. Springer T., Galfrè G., Secher D. S., Milstein C. Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens. Eur J Immunol. 1978 Aug;8(8):539–551. doi: 10.1002/eji.1830080802. [DOI] [PubMed] [Google Scholar]
  40. Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
  41. Taylor A. H., Haberman A. M., Gerhard W., Caton A. J. Structure-function relationships among highly diverse T cells that recognize a determinant from influenza virus hemagglutinin. J Exp Med. 1990 Dec 1;172(6):1643–1651. doi: 10.1084/jem.172.6.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Traunecker A., Dolder B., Karjalainen K. A novel approach for preparing anti-T cell receptor constant region antibodies. Eur J Immunol. 1986 Jul;16(7):851–854. doi: 10.1002/eji.1830160722. [DOI] [PubMed] [Google Scholar]
  44. Trowbridge I. S., Lesley J., Schulte R., Hyman R., Trotter J. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues. Immunogenetics. 1982 Mar;15(3):299–312. doi: 10.1007/BF00364338. [DOI] [PubMed] [Google Scholar]
  45. Tsubata T., Reth M. The products of pre-B cell-specific genes (lambda 5 and VpreB) and the immunoglobulin mu chain form a complex that is transported onto the cell surface. J Exp Med. 1990 Sep 1;172(3):973–976. doi: 10.1084/jem.172.3.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Uematsu Y., Ryser S., Dembić Z., Borgulya P., Krimpenfort P., Berns A., von Boehmer H., Steinmetz M. In transgenic mice the introduced functional T cell receptor beta gene prevents expression of endogenous beta genes. Cell. 1988 Mar 25;52(6):831–841. doi: 10.1016/0092-8674(88)90425-4. [DOI] [PubMed] [Google Scholar]
  47. Wegener A. M., Letourneur F., Hoeveler A., Brocker T., Luton F., Malissen B. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Cell. 1992 Jan 10;68(1):83–95. doi: 10.1016/0092-8674(92)90208-t. [DOI] [PubMed] [Google Scholar]
  48. Yagüe J., White J., Coleclough C., Kappler J., Palmer E., Marrack P. The T cell receptor: the alpha and beta chains define idiotype, and antigen and MHC specificity. Cell. 1985 Aug;42(1):81–87. doi: 10.1016/s0092-8674(85)80103-3. [DOI] [PubMed] [Google Scholar]
  49. 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]

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