Abstract
The H-2L d allele has been identified by others as the sole Ir gene in the H-2 d haplotype for the cytotoxic T lymphocyte (CTL) response to mouse lymphocytic choriomeningitis virus (LCMV). The BALB/c-H-2 dm2 (C-H-2 dm2) mutant lacks H-2L d, and thus should be ideal for assessing the contribution of virus-immune CTL to LCM immunopathology. Comparison of the C-H-2 dm2 mice with congenic BALB/c mice revealed that there is a delay of about 24 h in the onset of severe inflammatory process and symptoms in the mutant strain, but the absence of H-2L d did not prevent the later development of fatal disease in mice injected intracerebrally (i.e.) with neurotropic LCMV. This could indicate that virus-immune CTL are not the major mediators of clinical LCM. Spleen cells from LCMV-primed BALB/c mice did not show CTL activity for LCMV-infected C3H.OH, C-H-2 dm2, or (CBA × C-H-2 dm2)F1 target cells. However, immune lymphocytes from both the mutant and the F1 strains lyse virus-infected BALB/c cells. Furthermore, BtO.HTG and, in some experiments, B10.A(5R) mice generated CTL lytic for LCMV-infected BALB/c, C-H-2 dm2, and (CBA × CH-2 dm2)F1 macrophages. Apparently H-2L d is immunodominant in the H-2d restricted response to LCMV. However, in the absence of H-2L d, it seems that H-2K d and, to a lesser extent, H-2D d also serve as Ir genes for the CTL response in this infection. Even so, the absence of the H-2Ld-restricting element results in a disease process which is either delayed in onset or less severe.
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References
Allan, J. E. and Doherty, P. C.: Immune T cells can protect or induce fatal neurological disease in murine lymphocytic choriomeningitis. Cell Immunol. 90: 401–407, 1985
Allouche, M., Owen, J. A., and Doherty, P. C.: Limiting-dilution analysis of weak influenza-immune T cell responses associated with H-2Kb and H-21b. J. Immunol. 129: 689–693, 1982
Buchmeier, M. J., Welsh, R. M., Dutko, F. J., and Oldstone, M. B. A.: The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv. Immunol. 30: 275–331, 1980
Cole, G. A., Nathanson, N., and Prendergast, R. A.: Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature 238: 335–337, 1972
Dialynas, D. P., Wilde, D. B., Marrack, P., Pierres, A., Wall, K. A., Havran, W., Otten, G., Loken, M. R., Pierres, M., Kappler, J., and Fitch, F. W.: Characterization of the marine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: Expression of L3T4a functional T cell clones appears to correlate with class II MHC antigen reactivity. Immunol. Rev. 74: 29–56, 1983
Doherty, P. C.: Immunological surveillance: T cell repertoire and the biological function of MHC antigens. In G. Möller and E. Möller (eds.): Genetics of the Immune Response. Proceedings of the Nobel Symposium on Genetics of the Immune Response, pp. 91–109, Plenum Press, New York, 1983
Doherty, P. C.: T cells and viral infections. Brit. Med. Bull. 41: 7–14, 1984
Doherty, P. C. and Korngold, R.: Characteristics of pox-virus induced meningitis: Virus-specific and non-specific cytotoxic effectors in the inflammatory exudate. Scand. J. Immunol. 18: 1–7, 1983
Doherty, P. C. and Zinkernagel, R. M.: T cell-mediated immunopathology in viral infections. Transplant. Rev. 19: 89–120, 1974
Doherty, P. C. and Zinkernagel, R. M.: Capacity of sensitized thymus derived lymphocytes to induce fatal lymphocytic choriomeningitis is restricted by the H-2 gene complex. J. Immunol. 114: 30–33, 1975
Doherty, P. C., Blanden, R. V., and Zinkernagel, R. M.: Specificity of virus-immune effector T cells for H2K or H-2D compatible interactions: Implications for H-antigen diversity. Transplant. Rev. 29: 89–124, 1976
Doherty, P. C., Biddison, W. E., Bennink, J. R., and Knowles, B. B.: Cytotoxic T cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype. J. Exp. Med. 148: 534–543, 1978
Doherty, P. C., Knowles, B. B., and Wettstein, P. J.: Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell function. Adv. Cancer Res. 42: 1–65, 1984
Dunlop, M. B. C. and Blanden, R. V.: Secondary cytotoxic cell response to lymphocytic choriomeningitis virus. I. Kinetics of induction in vitro and yields of effector cells. Immunology 31: 171–180, 1976
Frelinger, J. A., Orn, A., Brayton, P. R., and Hood, L.: Use of cloned H-2 genes for study of H-2-restricted cytotoxicity: Ld is the LCMV restriction element for H-2d. Transplant. Proc. 15: 2024–2026, 1983
Ivanyi, D., Snoek, M., and Demant, P.: Demonstration of four new allelic products and independence of H-2D and H-2L molecules. Tissue Antigens 14: 233–250, 1979
Kaplan, D. R., Griffith, R., Braciale, V. L., and Braciale, T. J.: Influenza virus specific human cytotoxic T cell clones: Heterogeneity in antigenic specificity and restriction by class II MHC products. Cell Immunol. 88: 193–206, 1984
Marker, O., Thomsen, A. R., Volkert, M., Hansen, B. L., and Clemmensen, I. H.: High dose survival in the lymphocytic choriomeningitis virus infection is accompanied by suppressed DTH but unaffected T cell cytotoxicity. Scand. J. Immunol., in press, 1984
Meuer, S. C., Hodgdon, J. C., Cooper, D. A., Hussey, R. E., Fitzgerald, K. A., Schlossman, S. F., and Reinherz, E. L.: Human cytotoxic clones directed at autologous virus-infected targets: Further evidence for linkage of genetic restriction to T4 and T8 surface glycoproteins. J. Immunol. 131: 186–190, 1983
Müllbacher, A., Blanden, R. V., and Brenan, M.: Neonatal tolerance to major histocompatibility complex antigens alters Ir gene control of the cytotoxic T cell response to vaccinia virus. J. Exp. Med. 157: 1324–1338, 1983
Orn, A., Goodenow, R. S., Hood, L., Brayton, P. R., Woodward, J. G., Harman, R. C., and Frelinger, J. A.: Product of a transferred H-2Ld gene acts as a restriction element for LCMV-specific killer T cells. Nature 297: 415–417, 1982
Pfau, C. J., Valenti, J. K., Pevear, D. C., and Hunt, K. D.: Lymphocytic choriomeningitis virus killer T cells are lethal only in weakly disseminated murine infections. J. Exp. Med. 156: 79–89, 1982
Steinmetz, M. and Hood, L.: Genes of the major histocompatibility complex in mouse and man. Science 222: 727–733, 1983
Swain, S. L.: T cell subsets and the recognition of MHC class. Immunol. Rev. 74: 129–142, 1983
Thomsen, A. R., Bro-Jørgensen, K., and Volkert, M.: Fatal meningitis following lymphocytic choriomeningitis virus infection reflects delayed-type hypersensitivity rather than cytotoxicity. Scand. J. Immunol. 17: 139–145, 1983
Wong, G. H. W., Bartlett, P. F., Clark-Lewis, I., Battye, F., and Schrader, J. W.: Inducible expression of H-2 and Ia antigens on brain cells. Nature 310: 688–691, 1984
Zinkernagel, R. M. and Doherty, P. C.: Peritoneal macrophages as targets for measuring virus-specific T cell-mediated cytotoxicity in vitro. J. Immunol. Methods 8: 263–266, 1975
Zinkernagel, R. M., Althage, A., Cooper, S., Kreeb, G., Klein, P. A., Sefton, B., Flaherty, L., Stimpfling, J., Shreffler, D., and Klein, J.: Ir genes in H-2 regulate generation of antiviral cytotoxic T cells: Mapping to K or D and dominance of unresponsiveness. J. Exp. Med. 148: 592–606, 1978
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Allan, J.E., Doherty, P.C. Consequences of a single Ir-gene defect for the pathogenesis of lymphocytic choriomeningitis. Immunogenetics 21, 581–589 (1985). https://doi.org/10.1007/BF00395882
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DOI: https://doi.org/10.1007/BF00395882