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. 1989 Sep 1;170(3):901–912. doi: 10.1084/jem.170.3.901

Inhibition of MHC class II-restricted T cell response by Lyt-2 alloantigen

PMCID: PMC2189444  PMID: 2475576

Abstract

T cell hybridomas were established by fusing a CD8+ V beta 8.1+ CTL clone and a CD4+ V beta 8.1+ helper T lymphocyte (HTL) clone to the thymoma cell line BW5147. In contrast to the HTL x BW hybridomas, which retain the same antigen specificity as the original T cell clone, the CTL x BW hybridomas lost the class I MHC-restricted antigen response but acquired a new specificity to Mlsa antigen. Mlsa reactivity of CTL x BW hybridomas was shown to be mediated by the CTL TCR as assayed by inhibition using an anticlonotypic antibody to the CTL clone. Since hybridomas established with BW5147 lose CD8 expression, we have introduced the CD8 molecule into CTL x BW5147 hybridomas by gene transfection. The CD8+ V beta 8.1+ hybridoma was no longer capable of reacting to Mlsa antigen but exhibited the same antigen specificity as the parental CTL clone. Furthermore, the presence of the transfected CD8 molecule in the HTL x BW hybridomas was found to be inhibitory to class II MHC-restricted antigen reactivity. These results demonstrate that, besides its role in increasing the overall avidity of T cell- class I MHC/antigen interaction, the CD8 molecule inhibits T cell-class II MHC gene product/antigen interaction. This negative effect of the CD8 molecule on a class II MHC-restricted response may account for the failure of CD8+ T cells using either V beta 8.1 or V beta 6, which impart reactivity to the Mlsa antigen on CD4+ T cells, to respond to the Mlsa antigen.

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Selected References

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

  1. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  2. Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
  3. Ceredig R., Dialynas D. P., Fitch F. W., MacDonald H. R. Precursors of T cell growth factor producing cells in the thymus: ontogeny, frequency, and quantitative recovery in a subpopulation of phenotypically mature thymocytes defined by monoclonal antibody GK-1.5. J Exp Med. 1983 Nov 1;158(5):1654–1671. doi: 10.1084/jem.158.5.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dembić Z., Haas W., Zamoyska R., Parnes J., Steinmetz M., von Boehmer H. Transfection of the CD8 gene enhances T-cell recognition. Nature. 1987 Apr 2;326(6112):510–511. doi: 10.1038/326510a0. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Gabert J., Langlet C., Zamoyska R., Parnes J. R., Schmitt-Verhulst A. M., Malissen B. Reconstitution of MHC class I specificity by transfer of the T cell receptor and Lyt-2 genes. Cell. 1987 Aug 14;50(4):545–554. doi: 10.1016/0092-8674(87)90027-4. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [DOI] [PubMed] [Google Scholar]
  9. Janeway C. A., Jr, Katz M. E. The immunobiology of the T cell response to Mls-locus-disparate stimulator cells. I. Unidirectionality, new strain combinations, and the role of Ia antigens. J Immunol. 1985 Apr;134(4):2057–2063. [PubMed] [Google Scholar]
  10. Kanagawa O. Antibody-mediated activation of T cell clones as a method for screening hybridomas producing antibodies to the T cell receptor. J Immunol Methods. 1988 Jun 13;110(2):169–178. doi: 10.1016/0022-1759(88)90100-7. [DOI] [PubMed] [Google Scholar]
  11. Kanagawa O., Chiller J. M. Lymphokine-mediated induction of cytolytic activity in a T cell hybridoma. J Immunol. 1985 Jan;134(1):397–403. [PubMed] [Google Scholar]
  12. Kanagawa O., Palmer E., Bill J. The T cell receptor V beta 6 domain imparts reactivity to the Mls-1a antigen. Cell Immunol. 1989 Apr 1;119(2):412–426. doi: 10.1016/0008-8749(89)90255-4. [DOI] [PubMed] [Google Scholar]
  13. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  14. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
  16. MacDonald H. R., Hengartner H., Pedrazzini T. Intrathymic deletion of self-reactive cells prevented by neonatal anti-CD4 antibody treatment. Nature. 1988 Sep 8;335(6186):174–176. doi: 10.1038/335174a0. [DOI] [PubMed] [Google Scholar]
  17. Mathieson B. J., Fowlkes B. J. Cell surface antigen expression on thymocytes: development and phenotypic differentiation of intrathymic subsets. Immunol Rev. 1984 Dec;82:141–173. doi: 10.1111/j.1600-065x.1984.tb01121.x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Nakayama E., Shiku H., Stockert E., Oettgen H. F., Old L. J. Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1977–1981. doi: 10.1073/pnas.76.4.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  21. Reinherz E. L., Meuer S. C., Schlossman S. F. The human T cell receptor: analysis with cytotoxic T cell clones. Immunol Rev. 1983;74:83–112. doi: 10.1111/j.1600-065x.1983.tb01085.x. [DOI] [PubMed] [Google Scholar]
  22. Roehm N., Herron L., Cambier J., DiGuisto D., Haskins K., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells: distribution on thymus and peripheral T cells. Cell. 1984 Sep;38(2):577–584. doi: 10.1016/0092-8674(84)90512-9. [DOI] [PubMed] [Google Scholar]
  23. Rupp F., Acha-Orbea H., Hengartner H., Zinkernagel R., Joho R. Identical V beta T-cell receptor genes used in alloreactive cytotoxic and antigen plus I-A specific helper T cells. 1985 May 30-Jun 5Nature. 315(6018):425–427. doi: 10.1038/315425a0. [DOI] [PubMed] [Google Scholar]
  24. Scollay R., Bartlett P., Shortman K. T cell development in the adult murine thymus: changes in the expression of the surface antigens Ly2, L3T4 and B2A2 during development from early precursor cells to emigrants. Immunol Rev. 1984 Dec;82:79–103. doi: 10.1111/j.1600-065x.1984.tb01118.x. [DOI] [PubMed] [Google Scholar]
  25. Shinohara N., Sachs D. H. Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus. J Exp Med. 1979 Sep 19;150(3):432–444. doi: 10.1084/jem.150.3.432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Swain S. L. T cell subsets and the recognition of MHC class. Immunol Rev. 1983;74:129–142. doi: 10.1111/j.1600-065x.1983.tb01087.x. [DOI] [PubMed] [Google Scholar]
  27. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  28. 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]

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