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The Lyt-2 Accessory Molecule is Responsible for the Weak Mouse Anti-HLA Xeno-Response

  • G. J. Hämmerling
  • U. Kalinke
  • B. Arnold

Summary

For the last two decades it remained a puzzle why CTL responses to xeno MHC antigens (e. g. mouse anti-human HLA) were weak in comparison to the very strong allo-responses (H-2 against another H-2 allele). One possibility was that in mice the T cell repertoire was not positively selected towards the recognition of HLA molecules, due to the absence of HLA in mice. However, HLA-Cw3 transgenic mice mounted the same weak xeno-response against another HLA molecule (HLA-A2) as did normal mice. In further studies it was observed that the murine Lyt-2 molecule failed to interact with the a3 domain of the HLA class I molecule. Following this observation transgenic mice were constructed with an HLA/H-2 hybrid gene containing the a1 and a2 domains of HLA-B27 and the a3 domain of H-2KAd. Splenocytes from normal mice made a very strong xeno-response against the cells from the transgenic mice expressing the HLA/H-2 hybrid molecule. These findings show that the weak xeno-responses are due to the failure of the Lyt-2 molecules interact with HLA class I, and not to the selection of the mouse T cell repertoire.

Keywords

Transgenic Mouse Hybrid Gene Cell Repertoire Precursor Frequency Bulk Culture 
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. 1.
    Achour A., Beguue B., Gomard E., Paul P., Sayagh B., van Pel A. and Levy J.P. Eur. J. Immunol. 1985. 16: 597CrossRefGoogle Scholar
  2. 2.
    Bjorkman P.J., Saper M.A., Samraoui B., Bennett W.S., Strominger J.L. and Wiley D.C. Nature 1987. 329: 506PubMedCrossRefGoogle Scholar
  3. 3.
    Dembic Z., Haas W., Zamoyska R., Parnes J., Steinmetz M. and v. Boehmer H. Nature 1987. 326: 510PubMedCrossRefGoogle Scholar
  4. 4.
    Dill O., Kievits F., Koch S., Ivanyi P. and Hämmerling G.J. Proc. Natl. Acad. Sci. USA 1988. 85: 5664PubMedCrossRefGoogle Scholar
  5. 5.
    Dutton R.W., Panfili P.R. and Swain S.L. Immunological Rev. 1978. 42: 20CrossRefGoogle Scholar
  6. 6.
    Engelhard V.H., Strominger J.L., Mescher M. and Burakoff S. J. Proc. Natl. Acad. Sci. USA 1978. 75: 5688CrossRefGoogle Scholar
  7. 7.
    Gabert J., Langlet C., Zamoyska R., Parnes J., Schmitt-Verhulst A.-M. and Malissen, B. Cell 1987. 40: 545CrossRefGoogle Scholar
  8. 8.
    Hämmerling G.J., Hunt T., Dill O. and Moreno J. Eur. J. Immunol. 1989. 19: 599–604PubMedCrossRefGoogle Scholar
  9. 9.
    Hines D.L., Cowall C. and Lang R.W. Transplantation 1976. 21: 375PubMedCrossRefGoogle Scholar
  10. 10.
    Holterman M.J. and Engelhard V.H. Proc. Natl. Acad. Sci. USA 1986. 83: 9699PubMedCrossRefGoogle Scholar
  11. 11.
    Kievits F., Ivanyi P., Kripenfort P., Berns A. and Ploegh H.L. Nature 1987: 329: 447PubMedCrossRefGoogle Scholar
  12. 12.
    Klein J. 1986. “Natural History of the Major Histocompatibility Complex”. Nature of Alloreactivity: Frequency of Responding Cells. John Wiley and Sons, p. 417Google Scholar
  13. 13.
    Kourilsky P. and Claverie J.-M. Annal. Inst. Pasteur 1986. 137: D3Google Scholar
  14. 14.
    Marrack P. and Kappler, Immunol. Today 1988. 9: 285CrossRefGoogle Scholar
  15. 15.
    Maryanski J.L., Moretta A., Jordan B., De Plaen E., Van Pel A., Boon T. and Cerottini J.C. Eur. J. Immunol. 1985. 15: 1111PubMedCrossRefGoogle Scholar
  16. 16.
    Maryanski J.L., Accolla R.S. and Bertran J. J. Immunol. 1986. 136: 4340PubMedGoogle Scholar
  17. 17.
    Maryanski J.L., Pala P., Corradin G., Jordan B. and Cerottini J.C. Nature 1986. 578: 581Google Scholar
  18. 18.
    Maziarz R., Allen H., Strominger J.L., Flavell R., Biro P.A. and Burakoff S.J. Proc. Natl. Acad. Sci. USA 1985. 82: 6276–6280PubMedCrossRefGoogle Scholar
  19. 19.
    Moretta A., Pantaleo G., Mingari M.C., Moretta I. and Cerottini J.C. J. Exp. Med. 1980. 159: 921CrossRefGoogle Scholar
  20. 20.
    Potter T.A., Rajan T.V., Dick II R.F. and Bluestone J.A. Nature 1989. 337: 73–75PubMedCrossRefGoogle Scholar
  21. 21.
    Salter R.D., Norment A.M., Chen B.P., Clayberger C., Krensky A.M., Littman D.R. and Parham P. Nature 1989. 338: 345–347PubMedCrossRefGoogle Scholar
  22. 22.
    Shimonkevitz R., Luescher B., Cerottini J.-C. and MacDonald H.R. J. Immunol. 1985. 135: 892PubMedGoogle Scholar
  23. 23.
    Widmer M.B. and Bach F.H. J. Exp. Med. 1972. 135: 1204PubMedCrossRefGoogle Scholar
  24. 24.
    Wilson D.B. and Fox D.H. J. Exp. Med. 1971. 134: 857PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • G. J. Hämmerling
  • U. Kalinke
  • B. Arnold
    • 1
  1. 1.Institute for Immunology and GeneticsGerman Cancer Research CenterHeidelbergGermany

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