Single H2Kb, H2Db and double H2KbDb knockout mice: peripheral CD8+ T cell repertoire and antilymphocytic choriomeningitis virus cytolytic responses

Single H2Kb, H2Db and double H2KbDb homozygous knockout (KO) mice were generated and their peripheral CD8+ T cell repertoires compared to that of C57BL/6 (B6) mice. Limited (10 – 20 %, H2Db), substantial (30 – 50 %, H2Kb) and profound (90 %, H2KbDb) reduction of peripheral CD8+ T cells was observed in KO mice, without Vβ diversity alteration. Classical class Ia molecules therefore ensure most but not all of the peripheral CD8+ T cell repertoire education. As expected, H2Kb but also H2Db KO mice developed choriomeningitis following intracranial infection by lymphocytic choriomeningitis virus with the same kinetics, lethality and CD8+ cell implication as wild‐type B6 mice. By contrast, H2KbDb (class Ia–Ib+) KO mice survived. Choriomeningitis of H2Db KO mice was linked to the development of a subdominant (in normal B6 mice) H2Kb‐restricted cytotoxic T lymphocyte response. Mice expressing a restricted set of histocompatibility class I molecules should represent useful tools to evaluate the immunological potentials of individual MHC class I molecules.

[1]  P. Travers,et al.  Maturation of Qa-1b class I molecules requires beta 2-microglobulin but is TAP independent. , 1998, Journal of immunology.

[2]  H. Bouwer,et al.  MHC class Ib-restricted cells contribute to antilisterial immunity: evidence for Qa-1b as a key restricting element for Listeria-specific CTLs. , 1997, Journal of immunology.

[3]  D. Pappin,et al.  Qa‐1 interaction and T cell recognition of the Qa‐1 determinant modifier peptide , 1997, European journal of immunology.

[4]  M. Oldstone,et al.  The signal sequence of lymphocytic choriomeningitis virus contains an immunodominant cytotoxic T cell epitope that is restricted by both H-2D(b) and H-2K(b) molecules. , 1997, Virology.

[5]  F. Lemonnier,et al.  HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice , 1997, The Journal of experimental medicine.

[6]  J. Forman,et al.  Peptide binding to the class Ib molecule, Qa-1b. , 1997, Journal of immunology.

[7]  R. Cotter,et al.  Dominance of a single peptide bound to the class I(B) molecule, Qa-1b. , 1997, Journal of immunology.

[8]  R. Zamoyska,et al.  Unprimed T cells are inefficiently stimulated by glycosylphosphatidylinositol-linked H-2Kb because of its lipid anchor rather than defects in CD8 binding. , 1996, International immunology.

[9]  M. Oldstone,et al.  Optimal lymphocytic choriomeningitis virus sequences restricted by H-2Db major histocompatibility complex class I molecules and presented to cytotoxic T lymphocytes , 1995, Journal of virology.

[10]  H. Ploegh,et al.  Peptide influences the folding and intracellular transport of free major histocompatibility complex class I heavy chains , 1995, The Journal of experimental medicine.

[11]  S. Tonegawa,et al.  Differential reactivity of residual CD8+ T lymphocytes in TAP1 and β2‐microglobulin mutant mice , 1995 .

[12]  J. Cook,et al.  Induction of peptide-specific CD8+ CTL clones in beta 2-microglobulin-deficient mice. , 1995, Journal of immunology.

[13]  R. Cotter,et al.  Identification of a tap-dependent leader peptide recognized by alloreactive T cells specific for a class Ib antigen , 1994, Cell.

[14]  P. Walden,et al.  CD4+ and CD8+ alpha beta, and gamma delta T cells are cytotoxic effector cells of beta 2-microglobulin-deficient mice against cells having normal MHC class I expression. , 1994, Journal of immunology.

[15]  G. Anderson,et al.  Thymic epithelial cells provide unique signals for positive selection of CD4+CD8+ thymocytes in vitro , 1994, The Journal of experimental medicine.

[16]  Hans Hengartner,et al.  Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice , 1994, Nature.

[17]  U. Staerz,et al.  Thymic education--T cells do it for themselves. , 1994, Immunology today.

[18]  M. Sitkovsky,et al.  Development and antigen specificity of CD8+ cytotoxic T lymphocytes in beta 2-microglobulin-negative, MHC class I-deficient mice in response to immunization with tumor cells. , 1994, Journal of immunology.

[19]  R. Angeletti,et al.  A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides , 1994, The Journal of experimental medicine.

[20]  R. Glas,et al.  The CD8+ T cell repertoire in beta 2-microglobulin-deficient mice is biased towards reactivity against self-major histocompatibility class I , 1994, The Journal of experimental medicine.

[21]  J. Smith,et al.  Model for the in vivo assembly of nascent Ld class I molecules and for the expression of unfolded Ld molecules at the cell surface , 1993, The Journal of experimental medicine.

[22]  M. Teitell,et al.  The alpha 3 domain of the Qa-2 molecule is defective for CD8 binding and cytotoxic T lymphocyte activation , 1993, The Journal of experimental medicine.

[23]  J. Frelinger,et al.  Transfer of lymphocytic choriomeningitis disease in beta 2-microglobulin-deficient mice by CD4+ T cells. , 1993, International immunology.

[24]  P. Doherty,et al.  Lymphocytic choriomeningitis virus induces a chronic wasting disease in mice lacking class I major histocompatibility complex glycoproteins , 1993, Journal of Neuroimmunology.

[25]  H. Rammensee,et al.  Qa-2 molecules are peptide receptors of higher stringency than ordinary class I molecules , 1993, Nature.

[26]  S. Tonegawa,et al.  TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4−8+ T cells , 1992, Cell.

[27]  H. Ljunggren,et al.  Major histocompatibility complex class I-specific and -restricted killing of beta 2-microglobulin-deficient cells by CD8+ cytotoxic T lymphocytes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Bix,et al.  Functionally conformed free class I heavy chains exist on the surface of beta 2 microglobulin negative cells , 1992, The Journal of experimental medicine.

[29]  R. Kurlander,et al.  Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses. , 1992, Science.

[30]  E. Pamer,et al.  H-2M3 presents a listeria monocytogenes peptide to cytotoxic T lymphocytes , 1992, Cell.

[31]  J. Mcwhir,et al.  Gene targeting using a mouse HPRT minigene/HPRT-deficient embryonic stem cell system: Inactivation of the mouseERCC-1 gene , 1992, Somatic cell and molecular genetics.

[32]  J. Frelinger,et al.  LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. , 1992, Science.

[33]  S. Tonegawa,et al.  Highly restricted expression of the thymus leukemia antigens on intestinal epithelial cells , 1991, The Journal of experimental medicine.

[34]  J. Whitton,et al.  Vaccination and protection from a lethal viral infection: identification, incorporation, and use of a cytotoxic T lymphocyte glycoprotein epitope. , 1990, Virology.

[35]  Hidde L. Ploegh,et al.  Empty MHC class I molecules come out in the cold , 1990, Nature.

[36]  P. Marrack,et al.  Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. , 1990, Science.

[37]  R. Jaenisch,et al.  β2-Microglobulin deficient mice lack CD4−8+ cytolytic T cells , 1990, Nature.

[38]  I. Stroynowski Molecules related to class-I major histocompatibility complex antigens. , 1990, Annual review of immunology.

[39]  R. Zinkernagel,et al.  Major histocompatibility complex – dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease , 1989, European journal of immunology.

[40]  L. Hood,et al.  Epitope clusters of Qa-2 antigens defined by a panel of new monoclonal antibodies. , 1989, Journal of immunology.

[41]  J. Whitton,et al.  Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus-specific class I-restricted H-2Db cytotoxic T lymphocytes , 1988, The Journal of experimental medicine.

[42]  D. Moskophidis,et al.  Mechanism of recovery from acute virus infection: treatment of lymphocytic choriomeningitis virus-infected mice with monoclonal antibodies reveals that Lyt-2+ T lymphocytes mediate clearance of virus and regulate the antiviral antibody response , 1987, Journal of virology.

[43]  M. Monk,et al.  HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells , 1987, Nature.

[44]  R. Flavell,et al.  Beta 2-microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[45]  R. Ahmed,et al.  Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus. I. Generation and recognition of virus strains and H-2b mutants. , 1984, Journal of immunology.

[46]  R. Flavell,et al.  A nonpolymorphic class I gene in the murine major histocompatibility complex , 1984, Cell.

[47]  R. Cook,et al.  Expression of the thymus leukemia antigen by activated peripheral T lymphocytes , 1983, The Journal of experimental medicine.

[48]  M. Saron,et al.  Rapid enrichment of mouse natural killer cells by use of wheat germ agglutinin. , 1983, Journal of immunological methods.