H-2 Antigens pp 451-463 | Cite as

Epitopes of I-Ak Involved in Antigen Presentation to T-Cell Hybridomas

  • John H. Freed
  • Edward F. Rosloniec
  • Denise Gay
  • Laura J. Vitez
  • David J. McKean
  • Diane Mathis
Part of the NATO ASI Series book series (NSSA, volume 144)

Abstract

The discovery of MHC-restricted recognition of foreign antigens by cytotoxic and helper T lymphocytes marked a fundamental breakthrough in our understanding of antigen recognition by T cells and simultaneously provided the first convincing explanation for the physiologic function of MHC Class I and Class II molecules. However, fourteen years after the first description of MHC-restricted antigen recognition, the molecular details of the implied ternary complex involved in that recognition, i.e. processed antigen, MHC product, and T cell receptor, have yet to be described in depth. Primarily due to technical complexities of the system, it is only in the last two to three years that the problem has been examined at the biochemical level. Three basic approaches have been taken thus far. The first has been an examination of how the structure of the antigen itself influences the antigen presentation process, specifically which residues contact the T cell receptor or the Ia molecule (Ashwell et al. 1986, Guillet et al. 1986, Sette et al. 1987). The second approach has been to carry out molecular modelling of the T cell receptor in order to predict its potential binding sites (Novotny et al. 1986). The third approach has been to examine what effect Ia structure has on antigen presentation (Allen et al. 1985, Beck et al. 1986, Cohn et al. 1986, and Lechler et al. 1986) and specifically on the interaction of Ia with processed antigen (Buus et al. 1987) and with the T cell receptor. Our laboratories have recently adopted the third approach to dissecting the ternary complex of Ia, processed antigen and T cell receptor.

Keywords

Cell Receptor Antigen Presentation Hypervariable Region Direct Binding Assay Antigen Presenta 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Allen, P. M., McKean, D. J., Beck, B. N., Sheffield, J., and Glimcher, L. H.: Direct evidence that a class II molecule and a simple globular protein generate multiple determinants. J. Exp. Med. 162: 1264–1274, 1985PubMedCrossRefGoogle Scholar
  2. Amit, A. G., Mariuzza, R. A., Phillips, S. E. V., and Poljak, R. J.: Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science 233: 747–753, 1986.PubMedCrossRefGoogle Scholar
  3. Ashwell, J. D., Fox, B. S., and Schwartz, R. H.: Functional analysis of the interaction of the antigen-specific T cell receptor with its ligands. J. Immunol. 136: 757–768, 1986.PubMedGoogle Scholar
  4. Beck, B. N., Glimcher, L. H., Nilson, A. E., Pierres, M., and McKean, D. J.: The structure-function relationship of I-A molecules: Correlation of serologic and functional phenotypes of four I-Ak mutant cell lines. J. Immunol. 133: 3176–3182, 1984.PubMedGoogle Scholar
  5. Beck, B. N., Pease, L. R., Bell, M. P., Buerstedde, J. M., Nilson, A. E., Schlander, G. G., and McKean, D. J.: DNA sequence analysis of I-Aß mutants reveals serologically immunodominant region. J. Exp. Med. In press, 1987.Google Scholar
  6. Buus, S., Sette, A., Colon, S. M., Jenis, D. M., and Grey, H. M.: Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell 47: 1071–1077, 1986.PubMedCrossRefGoogle Scholar
  7. Buus, S., Sette, A., Colon, S. M., Miles, C., and Grey, H. M.: The relationship between MHC restriction and the capacity of Ia to bind immunogenic peptides. Science 235: 1353–1358, 1987.PubMedCrossRefGoogle Scholar
  8. Cohn, L. E., Glimcher, L. H., Waldmann, R. A., Smith, J. A., Ben-Nun, A., Seidman, J. G., and Choi, E.: Identification of functional regions on the I-Ab molecule by site-directed mutagenesis. Proc. Natl. Acad. Sci. U.S.A. 83: 747–751, 1986.PubMedCentralPubMedCrossRefGoogle Scholar
  9. Guillet, J. G., Lai, M. Z., Briner, T. J., Smith, J. A., and Gefter, M. L.: Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature 324: 260–262, 1986.PubMedCrossRefGoogle Scholar
  10. Kappler, J., White, J., Wegmann, D., Mustain, E., and Marrack, P.: Antigen presentation by la+ B cell hybridomas to H-2-restricted T cell hybridomas. Proc. Natl. Acad. Sci. U.S.A. 79: 3604–3607, 1982.PubMedCentralPubMedCrossRefGoogle Scholar
  11. Lechler, R. I., Ronchese, F., Braunstein, N. S., and Germain, R. N.: I-A-restricted T cell antigen recognition. Analysis of the roles of Aa and Aß using DNA-mediated gene transfer. J. Exp. Med. 163: 678696, 1986.Google Scholar
  12. Landais, D., Waltzinger, C., Beck, B. N., Staub, A., McKean, D. H., Benoist, C., and Mathis, D.: Functional sites on Ia molecules: A molecular dissection of Aa immunogenicity. Cell 47: 173–181, 1986.PubMedCrossRefGoogle Scholar
  13. Novotny, J., Tonegawa, S., Saito, H., Kranz, D. M., and Eisen, H. N.: Secondary, tertiary and quaternary structure of T-cell-specific immunoglobulin-like polypeptide chains. Proc. Natl. Acad. Sci. U.S.A. 83: 742–746, 1986.PubMedCentralPubMedCrossRefGoogle Scholar
  14. Sette, A., Buus, S., Colon, S., Smith, J. A., Miles, C., and Grey, H. M.: Structural characteristics of an antigen that are required for its interaction with Ia and recognition by T cells. Nature In press, 1987.Google Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • John H. Freed
    • 1
  • Edward F. Rosloniec
    • 1
  • Denise Gay
    • 1
  • Laura J. Vitez
    • 1
  • David J. McKean
    • 2
  • Diane Mathis
    • 3
  1. 1.National Jewish Center for Immunology and Respiratory MedicineDenverUSA
  2. 2.Department of ImmunologyMayo ClinicRochesterUSA
  3. 3.Laboratoire de Génétique Moléculaire des Eucaryotes du CNRSINSERMStrasbourg, CédexFrance

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