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. 1986 Sep;83(18):6998–7002. doi: 10.1073/pnas.83.18.6998

Expression of T3 in association with a molecule distinct from the T-cell antigen receptor heterodimer.

A Weiss, M Newton, D Crommie
PMCID: PMC386639  PMID: 3092224

Abstract

The T-cell antigen receptor consists of a disulfide-linked heterodimer (Ti) that is associated with another set of three nonpolymorphic, noncovalently linked peptides termed "T3." The cell surface expression of T3 has been thought to depend upon association with Ti. In this study, we demonstrate that T3 can be expressed in the absence of an associated Ti molecule on a T-cell leukemic line, PEER. Instead, on this cell line, T3 appears to be expressed in association with a 55- to 60-kDa glycoprotein that has a peptide backbone of 29 kDa. PEER fails to express Ti alpha-chain transcripts but does express Ti beta- and gamma-chain transcripts. Using a monoclonal antibody that reacts with nonpolymorphic epitopes expressed on Ti, WT31, we demonstrate that PEER fails to react with this antibody but does react with three independently derived anti-T3 antibodies. Moreover, a small subpopulation of T3-positive peripheral blood lymphocytes, like PEER, fails to express the antigenic determinants recognized by WT31. These results suggest that, on these normal lymphocytes, T3 may likewise be associated with a non-Ti molecule. The possibility that the 55- to 60-kDa molecule expressed on PEER, termed "Tp55-60," represents the protein product of the previously identified Ti gamma-chain gene is discussed.

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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. Allison J. P., Lanier L. L. Identification of antigen receptor-associated structures on murine T cells. Nature. 1985 Mar 7;314(6006):107–109. doi: 10.1038/314107a0. [DOI] [PubMed] [Google Scholar]
  3. Allison J. P., McIntyre B. W., Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982 Nov;129(5):2293–2300. [PubMed] [Google Scholar]
  4. Borst J., Prendiville M. A., Terhorst C. The T3 complex on human thymus-derived lymphocytes contains two different subunits of 20 kDa. Eur J Immunol. 1983 Jul;13(7):576–580. doi: 10.1002/eji.1830130712. [DOI] [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., 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]
  7. 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]
  8. Dialynas D. P., Murre C., Quertermous T., Boss J. M., Leiden J. M., Seidman J. G., Strominger J. L. Cloning and sequence analysis of complementary DNA encoding an aberrantly rearranged human T-cell gamma chain. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2619–2623. doi: 10.1073/pnas.83.8.2619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  10. Haskins K., Kubo R., White J., Pigeon M., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med. 1983 Apr 1;157(4):1149–1169. doi: 10.1084/jem.157.4.1149. [DOI] [PMC free article] [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. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Imboden J. B., Weiss A., Stobo J. D. The antigen receptor on a human T cell line initiates activation by increasing cytoplasmic free calcium. J Immunol. 1985 Feb;134(2):663–665. [PubMed] [Google Scholar]
  14. Kappler J., Kubo R., Haskins K., Hannum C., Marrack P., Pigeon M., McIntyre B., Allison J., Trowbridge I. The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: identification of constant and variable peptides. Cell. 1983 Nov;35(1):295–302. doi: 10.1016/0092-8674(83)90232-5. [DOI] [PubMed] [Google Scholar]
  15. Kinet J. P., Alcaraz G., Leonard A., Wank S., Metzger H. Dissociation of the receptor for immunoglobulin E in mild detergents. Biochemistry. 1985 Jul 16;24(15):4117–4124. doi: 10.1021/bi00336a046. [DOI] [PubMed] [Google Scholar]
  16. McIntyre B. W., Allison J. P. Biosynthesis and processing of murine T-cell antigen receptor. Cell. 1984 Oct;38(3):659–665. doi: 10.1016/0092-8674(84)90260-5. [DOI] [PubMed] [Google Scholar]
  17. Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Schlossman S. F., Reinherz E. L. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med. 1983 Feb 1;157(2):705–719. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Meuer S. C., Hodgdon J. C., Hussey R. E., Protentis J. P., Schlossman S. F., Reinherz E. L. Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J Exp Med. 1983 Sep 1;158(3):988–993. doi: 10.1084/jem.158.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morikawa S., Tatsumi E., Baba M., Harada T., Yasuhira K. Two E-rosette-forming lymphoid cell lines. Int J Cancer. 1978 Feb 15;21(2):166–170. doi: 10.1002/ijc.2910210207. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Oettgen H. C., Kappler J., Tax W. J., Terhorst C. Characterization of the two heavy chains of the T3 complex on the surface of human T lymphocytes. J Biol Chem. 1984 Oct 10;259(19):12039–12048. [PubMed] [Google Scholar]
  22. Oettgen H. C., Terhorst C., Cantley L. C., Rosoff P. M. Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx. Cell. 1985 Mar;40(3):583–590. doi: 10.1016/0092-8674(85)90206-5. [DOI] [PubMed] [Google Scholar]
  23. Ohashi P. S., Mak T. W., Van den Elsen P., Yanagi Y., Yoshikai Y., Calman A. F., Terhorst C., Stobo J. D., Weiss A. Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer. Nature. 1985 Aug 15;316(6029):606–609. doi: 10.1038/316606a0. [DOI] [PubMed] [Google Scholar]
  24. Quertermous T., Murre C., Dialynas D., Duby A. D., Strominger J. L., Waldman T. A., Seidman J. G. Human T-cell gamma chain genes: organization, diversity, and rearrangement. Science. 1986 Jan 17;231(4735):252–255. doi: 10.1126/science.3079918. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Ravid Z., Goldblum N., Zaizov R., Schlesinger M., Kertes T., Minowada J., Verbi W., Greaves M. Establishment and characterization of a new leukaemic T-cell line (Peer) with an unusual phenotype. Int J Cancer. 1980 Jun 15;25(6):705–710. doi: 10.1002/ijc.2910250604. [DOI] [PubMed] [Google Scholar]
  27. Reinherz E. L., Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Acuto O., Schlossman S. F. Comparison of T3-associated 49- and 43-kilodalton cell surface molecules on individual human T-cell clones: evidence for peptide variability in T-cell receptor structures. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4104–4108. doi: 10.1073/pnas.80.13.4104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. Tax W. J., Willems H. W., Reekers P. P., Capel P. J., Koene R. A. Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells. Nature. 1983 Aug 4;304(5925):445–447. doi: 10.1038/304445a0. [DOI] [PubMed] [Google Scholar]
  33. Van Wauwe J. P., De Mey J. R., Goossens J. G. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J Immunol. 1980 Jun;124(6):2708–2713. [PubMed] [Google Scholar]
  34. Weiss A., Imboden J., Shoback D., Stobo J. Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4169–4173. doi: 10.1073/pnas.81.13.4169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Yanagi Y., Chan A., Chin B., Minden M., Mak T. W. 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. Proc Natl Acad Sci U S A. 1985 May;82(10):3430–3434. doi: 10.1073/pnas.82.10.3430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. van den Elsen P., Shepley B. A., Borst J., Coligan J. E., Markham A. F., Orkin S., Terhorst C. Isolation of cDNA clones encoding the 20K T3 glycoprotein of human T-cell receptor complex. 1984 Nov 29-Dec 5Nature. 312(5993):413–418. doi: 10.1038/312413a0. [DOI] [PubMed] [Google Scholar]

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