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H-2 Antigens pp 671-679 | Cite as

Analysis of Anti-Reovirus Cytotoxic T Lymphocytes (CTL) Using the H-2dml Mutant

  • Duane W. Sears
  • Suezanne E. Parker
  • Donna Zeger
Part of the NATO ASI Series book series (NSSA, volume 144)

Abstract

The murine cytotoxic T lymphocyte response to reovirus -- a double-stranded, segmented RNA virus -- has been analyzed using the dm1 mutant and its d parent strain. Reovirus stimulates a strong CTL response in mice of both haplotypes. The H-2D/Ldm1, H-2Dd and H-2Ld antigens allserveas. anti-reovirus CTL restricting elements. These CTL most likely recognize nonmembrane structures of reovirus because this “naked” virus is nonenveloped and nonbudding with no known membrane maturation stage in its replication cycle. The fine-specificity of the H-2 restriction imposed by the individual class I molecules of these haplotypes has been examined by analyzing the crossreactivity patterns of parent and mutant CTL tested with L cells transformed with various cloned H-2 genes. Preliminary data indicates that d anti-reovirus CTL generally do not crossreact with infected targets expressing the mutant H-2D/Ldml antigen whereas dm1 antireovirus CTL frequently cross-lyse reovirus infected targets expressing either the H-Dd or H-Ld antigens. The nonreciprocity of the d and dm1 CTL response suggests that fundamentally different immunodominant determinants are selected for CTL recognition in d as compared to dm1 mice although substantial sequence homology exists between the H-2D/Ldml hybrid antigen and the two parent antigens from which the mutant class I molecule arose. Based on the unique hybrid nature of the H-2D/Ldml antigen, additional hybrid class I molecules have been constructed in collaboration with Drs. Iwona Stroynowski and Lee Hood, using the mutant and parent genes for exonshuffled gene constructs. Preliminary data is presented showing that dm1 CTL can recognize reovirus infected L cell transformants expressing the class I variant, [Dd]-[D/Ldml]-[Dd], with the brackets denotingtheboundaries between the [a1]-[m2]-[a3] extracellular domains. Eventually additional variants of this type will be constructed and expressed in L cells. In conjunction with the recently-isolated cloned reovirus genes, these novel class I genes will provide further insight into the structural elements of these molecules which govern anti-viral CTL recognition.

Keywords

Infected Target Major Histocompatibility Antigen Restricting Structure Parent Antigen Reovirus Protein 
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. Blanden, R. V., Dunlop, M. B. C., Doherty, P. C., and Kohn, H. I.: Effects of four H-2K mutations on virus-induced antigens recognized by cytotoxic T cells. Immunogenetics 3: 541–548, 1976CrossRefGoogle Scholar
  2. Burnside, S. S., P. Hunt, K. Ozato, and D. W. Sears. A molecular hybrid of the H-2D d and H-2L d genes expressed in the dm1 mutant. Proc. Natl. Acad. Sci. USA 81: 5204–5208, 1984.PubMedCrossRefGoogle Scholar
  3. Clark, S. S., and J. Forman. Allogeneic and associative recognition determinants of H-2 molecules. Transplant. Proc. 15: 2029020292, 1983.Google Scholar
  4. Egorov, I. K. A mutation of the histocompatibility-2 locus in the mouse. Genetika (Moscow) 3: 136–144, 1967.Google Scholar
  5. Egorov, I. K., and Z. K. Blandova. The genetic homogenicity of the inbred mice bred at the Stolbovya farm. II. Skin grafting tests. Geneteka 12:, 1968.Google Scholar
  6. Evans, G. A., D. H. Margulies, R. D. Camerini-Otero, K. Ozato, and J. G. Seidman. Structure and expression of a mouse majorhistocompatibility antigen gene, H-2L d . Proc. Natl. Acad. Sci. USA 79: 1994–1998, 1982a.PubMedCrossRefGoogle Scholar
  7. Evans, G. A., D. H. Margulies, B. Shykind, J. G. Seidman, and K. Ozato.Google Scholar
  8. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature 300: 755–757, 1982b.Google Scholar
  9. Goodenow, R. S., M. McMillan, M. Nicolson, B. T. Sher, K. Eakle, N. Davidson, and L. Hood. Identification of the class I genes of the mouse major histocompatibility complex by DNA-mediated gene transfer. Nature 300: 231–237, 1982a.PubMedCrossRefGoogle Scholar
  10. Goodenow, R. S., M. McMillan, A. Orn, M. Nicolson, N. Davidson, J. A. Frelinger, and L. Hood. Identification of a BALE/c H-2Ld gene by DNA-mediated gene transfer. Science 215: 677–679, 1982b.PubMedCrossRefGoogle Scholar
  11. Hood, L., M. Steinmetz, and B. Malissen. Genes of the major histocompatibility complex of the mouse. Ann. Rev. Immunol. 1: 529–568, 1983.CrossRefGoogle Scholar
  12. Hunt, P., S. S. Burnside, and D. W. Sears. Evidence of only one H-2D/L-related glycoprotein in H- 2am1 mutant cells. J. Immunogenet. 12: 33–44, 1985.PubMedCrossRefGoogle Scholar
  13. Kauffman, R. S., Lee, S., and Finberg, R.: Cytolytic T-cell mediated lysis of reovirus-infected cells: Requirements for infectious virus, viral particles and viral proteins in infected target cells. Virology 131: 265–273, 1983PubMedCrossRefGoogle Scholar
  14. Margulies, D. H., G. A. Evans, K. Ozato, R. D. Camerini-Otero, K. Tanaka, E. Appella, and J. G. Seidman. Expression of H-2Dd and H-2Ld mouse major histocompatibility antigen genes in L cells after DNA-mediated gene transfer. J. Immunol. 130: 463–470, 1983.PubMedGoogle Scholar
  15. Moore, K. W., B. T. Sher, Y. H. Sun, K. A. Eakle, and L. Hood. DNA sequence of a gene encoding a BALE/c mouse Ld transplantation antigen. Science 215: 679–682, 1982.PubMedCrossRefGoogle Scholar
  16. Murre, C., E. Choi, J. Weis, J. G. Seidman, K. Ozato, L. Liu, S. J. Burakoff, and C. S. Reiss. Dissection of serological and cytolytic T lymphocyte epitopes on murine major histocompatibility antigens by a recombinant H-2 gene separating the first two external domains. J. Exp. Med. 160: 167–178, 1984.PubMedCrossRefGoogle Scholar
  17. Ozato, K., G. A. Evans, B. Shykind, D. H. Margulies, and J. G. Seidman. Hybrid H-2 histocompatibility gene products assign domains recognized by alloreactive T cells. Proc. Natl. Acad. Sci. USA 80: 2040–2043, 1983.CrossRefGoogle Scholar
  18. Parker, S. E. Characterization of the murine CTL Response to Reovirus. Ph.D. Thesis, UCSB, 1987.Google Scholar
  19. Reiss, C. S., G. A. Evans, D. H. Margulies, J. G. Seidman, and S. J. Burakoff. Allospecific and virus-specific cytolytic T lymphocytes are restricted to the N or Cl domain of H-2 antigens expressed on L cells after DNA-mediated gene transfer. Proc. Natl. Acad. Sci. USA 80: 2709–2712, 1983.PubMedCentralPubMedGoogle Scholar
  20. Reiss, C. S., G. A. Evans, C. Murre, D. H. Margulies, J. G. Seidman, and S. J. Burakoff. Cytotoxic T lymphocyte recognition of class I H-2 antigens after DNA-mediated gene transfer. Fed. Proc. 43: 271–275, 1984PubMedGoogle Scholar
  21. Schwartz, R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Ann. Rev. Immunol. 3: 237–261, 1985.CrossRefGoogle Scholar
  22. Shumova, T. E., V. P. Kryshkina, and I. K. Egorov. Study of H-2 mutations in mice. I. Analysis of the mutation 504 by the F1 hybrid test. Genetika (Moscow) 8: 171–173, 1972.Google Scholar
  23. Stroynowski, I., S. Clark, L. A. Henderson, L. Hood, M. McMillan, and J. Forman. Interaction of al with a2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells. J. Immunol. 135: 2160–2166, 1985.PubMedGoogle Scholar
  24. Stroynowski, I., A. Orn, R. S. Goodenow, M. McMillan, J. Forman, P. R. Brayton, J. Frelinger, and L. Hood. Cytotoxic T lymphocytes recognize determinants on the BALB/c-H- 2Ld molecule controlled by al and a2 but not a3 external domains. Immunogenetics 20: 141–154, 1984PubMedCrossRefGoogle Scholar
  25. Sun, Y. H., R. S. Goodenow, and L. Hood. Molecular basis of the dml mutation in the major histocompatibility complex of the mouse: a D/L hybrid gene. J. Exp. Med. 162: 1588–1602, 1985.PubMedCrossRefGoogle Scholar
  26. Vedernikov, A. A., and I. K. Egorov. Study of H-2 mutations in mice. II. Recombination analysis of the mutation 504. Genetika (Moscow) 9: 60–66, 1973.Google Scholar
  27. Wilson, P. H., R. Nairn, S. G. Nathenson, and D. W. Sears. Unexpected complexity of the dm1 mutation revealed in the structure of three H-2D/L-related antigens. Immunogenetics 15: 225–237, 1982.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Duane W. Sears
    • 1
  • Suezanne E. Parker
    • 1
  • Donna Zeger
    • 1
  1. 1.Department of Biological SciencesUniversity of CaliforniaSanta BarbaraUSA

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