Virus specificity of cytotoxic T lymphocytes generated during acute lymphocytic choriomeningitis virus infection: role of the H-2 region in determining cross-reactivity for different lymphocytic choriomeningitis virus strains

We have compared the relatedness of five different strains of lymphocytic choriomeningitis virus (LCMV) as assessed by LCMV-specific cytotoxic T lymphocytes (CTL). Several different mouse strains were injected with each of the five LCMV strains, and the cross-reactivity of virus-specific CTL generated during the acute infection was tested by killing on a panel of target cells infected with the various LCMV strains. We found that the cross-reactivity pattern of LCMV-specific CTL generated in mice of H-2d haplotype (BALB/c WEHI and DBA/2) was strikingly different from that in mice of H-2b haplotype (C57BL/6 and C3H.Sw/Sn), suggesting that the fine specificity of LCMV-specific CTL is a function of the H-2 region. The characteristic cross-reactivity patterns were also observed in (C57BL/6 X DBA/2)F1 mice, demonstrating that the repertoire of the H-2b- and H-2d-restricted LCMV-specific CTL is not changed as a result of complementation by gene products of the other major histocompatibility haplotype. Studies with congenic BALB.B10 and (BALB.B10 X BALB/c)F1 mice firmly established that the characteristic cross-reactivity patterns of LCMV-specific CTL map to the H-2 region and are not influenced by background genes outside the major histocompatibility locus. These results suggest that LCMV determinants seen in the context of H-2d-restricting elements are different from those seen in the context of H-2b-restricting elements. Moreover, our studies show that CTL can be used as probes for dissecting differences among various LCMV strains, but the degree of relatedness between the different LCMV strains is not absolute when measured by CTL recognition. Since the H-2 region regulates the fine specificity of CTL generated during LCMV infection in its natural host, the degree of cross-protective immunity developed during a viral infection apparently depends on the major histocompatibility haplotype. The importance of these findings lies in understanding susceptibility or resistance of various host populations to viral infections and in designing vaccination programs to provide immunity.

[1]  A. Vitiello,et al.  Recognition of influenza-infected cells by cytolytic T lymphocyte clones: determinant selection by class I restriction elements. , 1983, Journal of immunology.

[2]  M. Oldstone,et al.  Genomic and biological variation among commonly used lymphocytic choriomeningitis virus strains. , 1983, The Journal of general virology.

[3]  D. Moskophidis,et al.  The immune response of the mouse to lymphocytic choriomeningitis virus. III. Differences of numbers of cytotoxic T lymphocytes in spleens of mice of different strains. , 1983, Cellular immunology.

[4]  J. Skehel,et al.  Influenza A specific cytotoxic T-cell clones that do not recognize viral glycoproteins , 1982, Nature.

[5]  D. Spriggs,et al.  Host immune response to reovirus: CTL recognize the major neutralization domain of the viral hemagglutinin. , 1982, Journal of immunology.

[6]  W G Laver,et al.  Molecular mechanisms of variation in influenza viruses , 1982, Nature.

[7]  B. Benacerraf,et al.  Induction, Control and Consequences of Virus Specific Cytotoxic T Cells , 1981, Immunological reviews.

[8]  K. Rosenthal,et al.  Experiments and Speculation on Antiviral Specificity of T and B Cells , 1981, Immunological reviews.

[9]  H. Ertl,et al.  An Analysis of Effector T Cell Generation and Function in Mice Exposed to Influenza A or Sendai Viruses , 1981, Immunological reviews.

[10]  Y. L. Lin,et al.  Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed- type hypersensitivity reactions , 1981, The Journal of experimental medicine.

[11]  M. Buchmeier,et al.  Monoclonal antibodies to lymphocytic choriomeningitis and pichinde viruses: generation, characterization, and cross-reactivity with other arenaviruses. , 1981, Virology.

[12]  T. Braciale,et al.  Heterogeneity and specificity of cloned lines of influenza-virus specific cytotoxic T lymphocytes , 1981, The Journal of experimental medicine.

[13]  R. Zinkernagel,et al.  Inability of mice to generate cytotoxic T lymphocytes to vesicular stomatitis virus restricted to H-2Kk or H-2Dk. , 1981, Journal of immunology.

[14]  M. Röllinghoff,et al.  H‐2‐linked murine cytotoxic T cell responses specific for sendai virus‐infected cells , 1978, European journal of immunology.

[15]  P. Doherty,et al.  Involvement of H-2L gene products in virus-immune T-cell recognition. Evidence for an H-2L-restricted T-cell response , 1978, The Journal of experimental medicine.

[16]  J. Klein,et al.  Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness , 1978, The Journal of experimental medicine.

[17]  J. Bennink,et al.  Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype , 1978, The Journal of experimental medicine.

[18]  R. Germain,et al.  The Immune Response Genes of the Major Histocompatibility Complex , 1978, Immunological reviews.

[19]  R. Zinkernagel,et al.  H-2 compatibility requirement for virus-specific T cell-mediated effector functions in vivo. I. Specificity of T cells conferring antiviral protection against lymphocytic choriomeningitis virus is associated with H-2K and H-2D. , 1976, Journal of immunology.

[20]  R. Zinkernagel,et al.  Inflammatory process in murine lymphocytic choriomeningitis is maximal in H-2K or H-2D compatible interactions. , 1976, Journal of immunology.

[21]  G. Shearer,et al.  Bifunctional major histocompatibility-linked genetic regulation of cell- mediated lympholysis to trinitrophenyl-modified autologous lymphocytes , 1975, The Journal of experimental medicine.

[22]  H. Mcdevitt,et al.  GENETIC CONTROL OF THE IMMUNE RESPONSE , 1974, The Journal of experimental medicine.

[23]  R. Zinkernagel,et al.  Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system , 1974, Nature.

[24]  O. Marker,et al.  STUDIES ON CELL-MEDIATED IMMUNITY TO LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN MICE , 1973, The Journal of experimental medicine.

[25]  R. Blanden,et al.  Antiviral Action of Immune Lymphocytes in Mice Infected with Lymphocytic Choriomeningitis Virus , 1972, Infection and Immunity.

[26]  B. Benacerraf,et al.  STUDIES ON ARTIFICIAL ANTIGENS : III. THE GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAPTEN-POLY-L-LYSINE CONJUGATES IN GUINEA PIGS , 1963 .

[27]  D. Faller,et al.  Cytotoxic T lymphocyte recognition of transfected cells expressing a cloned retroviral gene , 1983, Nature.

[28]  A. Vitiello,et al.  T-cell and B-cell responses to viral antigens at the clonal level. , 1983, Annual review of immunology.

[29]  M. Buchmeier,et al.  The virology and immunobiology of lymphocytic choriomeningitis virus infection. , 1980, Advances in immunology.

[30]  R M Zinkernagel,et al.  MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. , 1979, Advances in immunology.

[31]  H. Weiner,et al.  Generation of cytolytic T lymphocytes after reovirus infection: role of S1 gene. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[32]  I. Pedersen,et al.  Structural components and replication of arenaviruses. , 1979, Advances in virus research.

[33]  M. Oldstone.  Immune Responses, Immune Tolerance, and Viruses , 1979 .

[34]  C. Henney,et al.  In Vitro Correlates of LCM Virus-Induced Immune Response , 1973 .

[35]  N. Nathanson,et al.  Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. , 1972, Nature.

[36]  H. Mcdevitt,et al.  The Histocompatibility-Linked Immune Response Genes , 1975 .