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

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


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.


Transgenic Mouse Hybrid Gene Cell Repertoire Precursor Frequency Bulk Culture 
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  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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