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. 1986 Oct;83(19):7424–7428. doi: 10.1073/pnas.83.19.7424

Expression of T-cell-activating protein in peripheral lymphocyte subsets.

E T Yeh, H Reiser, B Benacerraf, K L Rock
PMCID: PMC386730  PMID: 3020545

Abstract

T-cell-activating protein (TAP) is an allelic 12-kDa membrane protein that participates in T-cell activation. Soluble anti-TAP monoclonal antibodies can trigger antigen-specific, major histocompatibility complex-restricted T-cell hybridomas to produce interleukin 2 and are mitogenic for normal T cells and thymocytes. TAP is expressed on 10% of thymocytes, which are mainly cortisone-resistant and mature. In the periphery, TAP is expressed on 70% of resting T cells but not on resting B cells. In this report, we analyze in detail the nature of TAP expression on peripheral lymphocyte subsets by immunofluorescence techniques. We show that all inducer (L3T4+) T cells are TAP+. In contrast, only 50% of Lyt-2+ T cells express detectable TAP. Functional studies demonstrated that at least part of the heterogeneity of TAP expression is present in the Lyt-2+ cytolytic T-cell (CTL) subset. Unstimulated CTL precursors are TAP- but are induced to express TAP in the effector state. Furthermore, this reflects actual synthesis of TAP, as TAP is detectable on activated Lyt-2+ CTLs passaged in vitro under conditions where passive acquisition can be ruled out. To extend this observation, we have studied the expression of TAP on activated T and B cells. Upon activation, all T and B cells became TAP+. Furthermore, the TAP molecules on B and T cells are indistinguishable by NaDodSO4/polyacrylamide gel electrophoresis. This suggests that TAP expression defines further heterogeneity of lymphocytes, with activation being one parameter influencing its expression.

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Selected References

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

  1. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4535–4539. doi: 10.1073/pnas.78.7.4535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  4. Greenstein J. L., Kappler J., Marrack P., Burakoff S. J. The role of L3T4 in recognition of Ia by a cytotoxic, H-2Dd-specific T cell hybridoma. J Exp Med. 1984 Apr 1;159(4):1213–1224. doi: 10.1084/jem.159.4.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gunter K. C., Malek T. R., Shevach E. M. T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4. J Exp Med. 1984 Mar 1;159(3):716–730. doi: 10.1084/jem.159.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Haustein D., Marchalonis J. J., Harris A. W. Immunoglobulin of T lymphoma cells. Biosynthesis, surface representation, and partial characterization. Biochemistry. 1975 May 6;14(9):1826–1834. doi: 10.1021/bi00680a004. [DOI] [PubMed] [Google Scholar]
  8. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  9. Kimura S., Tada N., Liu-Lam Y., Hämmerling U. Studies of the mouse Ly-6 alloantigen system. II. Complexities of the Ly-6 region. Immunogenetics. 1984;20(1):47–56. doi: 10.1007/BF00373446. [DOI] [PubMed] [Google Scholar]
  10. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Mizuochi T., Golding H., Rosenberg A. S., Glimcher L. H., Malek T. R., Singer A. Both L3T4+ and Lyt-2+ helper T cells initiate cytotoxic T lymphocyte responses against allogenic major histocompatibility antigens but not against trinitrophenyl-modified self. J Exp Med. 1985 Aug 1;162(2):427–443. doi: 10.1084/jem.162.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Reiser H., Yeh E. T., Gramm C. F., Benacerraf B., Rock K. L. Gene encoding T-cell-activating protein TAP maps to the Ly-6 locus. Proc Natl Acad Sci U S A. 1986 May;83(9):2954–2958. doi: 10.1073/pnas.83.9.2954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rock K. L., Benacerraf B. The role of Ia molecules in the activation of T lymphocytes. IV. The basis of the thymocyte IL 1 response and its possible role in the generation of the T cell repertoire. J Immunol. 1984 Apr;132(4):1654–1662. [PubMed] [Google Scholar]
  16. Rock K. L., Yeh E. T., Gramm C. F., Haber S. I., Reiser H., Benacerraf B. TAP, a novel T cell-activating protein involved in the stimulation of MHC-restricted T lymphocytes. J Exp Med. 1986 Feb 1;163(2):315–333. doi: 10.1084/jem.163.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Roopenian D. C., Orosz C. G., Bach F. H. Responses against single minor histocompatibility antigens. II. Analysis of cloned helper T cells. J Immunol. 1984 Mar;132(3):1080–1084. [PubMed] [Google Scholar]
  18. Roopenian D. C., Widmer M. B., Orosz C. G., Bach F. H. Helper cell-independent cytolytic T lymphocytes specific for a minor histocompatibility antigen. J Immunol. 1983 Feb;130(2):542–545. [PubMed] [Google Scholar]
  19. Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]
  20. Swain S. L. Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize class 1 major histocompatibility complex antigens regardless of their function. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7101–7105. doi: 10.1073/pnas.78.11.7101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sy M. S., Lee S. H., Tsurufuji M., Rock K. L., Benacerraf B., Finberg R. Two distinct mechanisms regulate the in vivo generation of cytotoxic T cells. J Exp Med. 1982 Sep 1;156(3):918–923. doi: 10.1084/jem.156.3.918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thomas J. O., Kornberg R. D. An octamer of histones in chromatin and free in solution. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2626–2630. doi: 10.1073/pnas.72.7.2626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ucker D. S., Kurasawa Y., Tonegawa S. An unusual clonotypic determinant on a cytotoxic T lymphocyte line is encoded by an immunoglobulin heavy chain variable region gene. J Immunol. 1985 Dec;135(6):4204–4214. [PubMed] [Google Scholar]
  24. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
  25. Woody J. N. Ly-6 is a T-cell differentiation antigen. Nature. 1977 Sep 1;269(5623):61–63. doi: 10.1038/269061a0. [DOI] [PubMed] [Google Scholar]
  26. Yeh E. T., Reiser H., Benacerraf B., Rock K. L. The expression, function, and ontogeny of a novel T cell-activating protein, TAP, in the thymus. J Immunol. 1986 Aug 15;137(4):1232–1238. [PubMed] [Google Scholar]

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