Lymphocyte Development in Mice Deficient for MHC Class I Expression

  • David H. Raulet
  • Nan-Shih Liao
  • Isabel Correa
  • Mark Bix
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 323)


The role of MHC Class I molecules in recognition of antigens by CD8+ T cells is well established, as is their role in the development of CD8+ T cells. The study of animals unable to normally express class I molecules provides an approach to learn about the role of class I molecules not only in CD8+ T cell development, but possibly in other cell types as well. This can be accomplished by analysis of mice mutant for the light chain of class I MHC, β2-microglobulin, which is necessary for normal functional cell surface expression of class I molecules. Such mice were produced in two laboratories by substitution of the normal β2-microglobulin gene for a mutant one, by homologous recombination embryonic stem cells, which were allowed to repopulate the germ line in chimeric mice 1, 2, 3, 4. In previous studies, we and others reported that mice homozygous for the mutant β2-m gene have severely diminished cell surface expression of MHC-I molecules, and are severely deficient in the production of functional, mature CD8+CD4- T cells 2,4. In this article, we summarize our recent work on the role of MHC-I molecules in development of CD8+ T cells, CD4-CD8-∝β+ T cells, and γδ+ T cells. In addition the role of MHC-I molecules in the development of natural killer (NK) cells is discussed.


Natural Killer Natural Killer Cell Natural Killer Activity Chimeric Mouse Thymic Epithelial Cell 
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  1. 1.
    M. Zijlstra, E. Li, F. Sajjadi, S. Subramani and R. Jaenisch. Germ-line transmission of a disrupted β2-microglobulin gene produced by homologous recombination in embryonic stem cells. Nature 342, 435 (1989).Google Scholar
  2. 2.
    M. Zijlstra, M. Bix, N.E. Simister, J.M. Loring, D.H. Raulet and R. Jaenisch. β2-Microglobulin deficient mice lack CD4 -8+ cytolytic T cells. Nature 344, 742 (1990).Google Scholar
  3. 3.
    B.H. Koller and O. Smithies. Inactivating the β2-microglobulin locus in mouse embryonic stem cells by homologous recombination. Proc. Natl. Acad. Sci. USA 86, 8932 (1989).Google Scholar
  4. 4.
    B.H. Koller, P. Marrack, J.W. Kappler and O. Smithies. Normal development of mice deficient in β2M, MHC class I proteins, and CD8+ T cells. Science 248, 1227 (1990).Google Scholar
  5. 5.
    B.J. Fowlkes, A.M. Kruisbeek, H. Hon-that, M.A. Weston, J.E. Coligan, R.H. Schwartz and D.M. Pardoll. A novel population of T-cell receptor ∝β-bearing thymocytes which predominantly expresses a single Vβ gene family. Nature 329, 251 (1987).Google Scholar
  6. 6.
    R.C. Budd, G.c. Meischer, R.C. Howe, R.K. Lees, C. Bron and H.R. MacDonald. Developmentally regulated expression of T cell receptor β chain variable domains in immature thymocytes. J. Exp. Med. 166, 577 (1987).Google Scholar
  7. 7.
    L.A. Matis, R. Cron and I.A. Bluestone. Major histocompatibility complex linked specificity of γδ receptor bearing T lymphocytes. Nature 330, 263 (1987).Google Scholar
  8. 8.
    M. Bonneville, K. Ito, E.G. Krecko, S. Itohara, D. Kappes, I. Ishida, O. Kanagawa, C.A. Janeway Jr., D.B. Murphy and S. Tonegawa. Recognition of a self major histocompatibility complex TL region product by γδ T-cell receptors. Proc. Natl. Acad. Sci. USA 86, 5928 (1989).Google Scholar
  9. 9.
    S. Porcelli, M.B. Brenner, J.L. Greenstein, S.P. Balk, C. Terhorst and P.A. Bleicher. Recognition of a cluster differentiation 1 antigen by human CD4-CD8-cytolytic T lymphocytes. Nature 341, 447 (1989).Google Scholar
  10. 10.
    F. Wells, S.-J. Gahm, S. Hedrick, I. Bluestone, A. Dent and L. Matis. Requirement for positive selection of yo receptor-bearing T cells. Science 253, 903 (1991).Google Scholar
  11. 11.
    P. Pereira, M. Zijlstra, J. McMmaster, J.M. Loring, R. Jaenisch and S. Tonegawa. Blockade of transgenic gamma delta T cell development in beta-2-microglobulin deficient mice. EMBO J. 11, 25 (1992).Google Scholar
  12. 12.
    I. Correa, M. Bix, N.-S. Liao, M. Zijlstra, R. Jaenisch and D. Raulet. Most γδ T cells developed normally in β2-microglobulindeficient mice. Proc. Natl. Acad. Sci. USA 89, 653 (1992).Google Scholar
  13. 13.
    K. Karre, H.G. Ljunggren, G. Piontek and R. Kiessling. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319, 675 (1986).Google Scholar
  14. 14.
    W.J. Storkus, D.N. Howell, R.D. Salter, J.R. Dawson and P. Cresswell. NK susceptibility varies inversely with target cell class I HLA antigen expression. J. Immunol. 138, 1657 (1987).Google Scholar
  15. 15.
    M. Bix, N.-S. Liao, M. Zijlstra, J. Loring, R. Jaenisch and D. Raulet. Rejection of class I MHC-deficient hemopoietic cells by irradiated MHC-matched mice. Nature 349, 329 (1991).Google Scholar
  16. 16.
    N. Liao, M. Bix, M. Zijlstra, R. Jaenisch and D. Raulet. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science 253, 199 (1991).Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • David H. Raulet
    • 1
  • Nan-Shih Liao
    • 1
  • Isabel Correa
    • 1
  • Mark Bix
    • 1
  1. 1.Department of Molecular and Cell Biology, Division of Immunology, 489 LSAUniversity of CaliforniaBerkeleyUSA

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