Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Jul 1;170(1):269–277. doi: 10.1084/jem.170.1.269

Major histocompatibility complex-linked susceptibility or resistance to disease caused by a noncytopathic virus varies with the disease parameter evaluated

PMCID: PMC2189361  PMID: 2746160

Abstract

The influence of major transplantation antigens on susceptibility to T cell-mediated disease caused by infection with the noncytopathic virus lymphocytic choriomeningitis virus (LCMV) was evaluated in B10 H-2- congenic mice. Susceptibility to early T cell-mediated liver cell destruction (day 7-9) and early mortality (before day 12) was H-2Dq linked and correlated directly with early (day 6-8) and high cytotoxic T cell activity. In contrast, susceptibility to become an LCMV carrier, inability to rapidly clear virus, or tendency to develop late hepatitis (day 14-17) was linked to Dk and correlated with absence of early cytotoxic T cell activity. Thus, H-2D-regulated T cell-immune responses controlling both virus spread and immunopathology may directly determine the type and severity of disease. The results illustrate that susceptibility to disease caused by one virus may be linked to distinct MHC alleles dependent upon the disease parameter studied.

Full Text

The Full Text of this article is available as a PDF (636.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahmed R., Salmi A., Butler L. D., Chiller J. M., Oldstone M. B. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J Exp Med. 1984 Aug 1;160(2):521–540. doi: 10.1084/jem.160.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bianchi L. The immunopathology of acute type B hepatitis. Springer Semin Immunopathol. 1981 Apr;3(4):421–438. doi: 10.1007/BF01951491. [DOI] [PubMed] [Google Scholar]
  3. Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
  4. Cole G. A., Nathanson N., Prendergast R. A. Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature. 1972 Aug 11;238(5363):335–337. doi: 10.1038/238335a0. [DOI] [PubMed] [Google Scholar]
  5. Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
  6. Guillet J. G., Lai M. Z., Briner T. J., Buus S., Sette A., Grey H. M., Smith J. A., Gefter M. L. Immunological self, nonself discrimination. Science. 1987 Feb 20;235(4791):865–870. doi: 10.1126/science.2433769. [DOI] [PubMed] [Google Scholar]
  7. HOTCHIN J. The biology of lymphocytic choriomeningitis infection: virus-induced immune disease. Cold Spring Harb Symp Quant Biol. 1962;27:479–499. doi: 10.1101/sqb.1962.027.001.046. [DOI] [PubMed] [Google Scholar]
  8. Jacobson S., Pfau C. J. Viral pathogenesis and resistance to defective interfering particles. Nature. 1980 Jan 17;283(5744):311–313. doi: 10.1038/283311a0. [DOI] [PubMed] [Google Scholar]
  9. Lehmann-Grube F., Assmann U., Löliger C., Moskophidis D., Löhler J. Mechanism of recovery from acute virus infection. I. Role of T lymphocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice. J Immunol. 1985 Jan;134(1):608–615. [PubMed] [Google Scholar]
  10. McDevitt H. O., Bodmer W. F. HL-A, immune-response genes, and disease. Lancet. 1974 Jun 22;1(7869):1269–1275. doi: 10.1016/s0140-6736(74)90021-x. [DOI] [PubMed] [Google Scholar]
  11. McIntyre K. W., Welsh R. M. Accumulation of natural killer and cytotoxic T large granular lymphocytes in the liver during virus infection. J Exp Med. 1986 Nov 1;164(5):1667–1681. doi: 10.1084/jem.164.5.1667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mondelli M., Eddleston A. L. Mechanisms of liver cell injury in acute and chronic hepatitis B. Semin Liver Dis. 1984 Feb;4(1):47–58. doi: 10.1055/s-2008-1040645. [DOI] [PubMed] [Google Scholar]
  13. Oldstone M. B., Dixon F. J., Mitchell G. F., McDevitt H. O. Histocompatibility-linked genetic control of disease susceptibility. Murine lymphocytic choriomeningitis virus infection. J Exp Med. 1973 May 1;137(5):1201–1212. doi: 10.1084/jem.137.5.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Oldstone M. B., Whitton J. L., Lewicki H., Tishon A. 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. J Exp Med. 1988 Aug 1;168(2):559–570. doi: 10.1084/jem.168.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pfau C. J., Valenti J. K., Pevear D. C., Hunt K. D. Lymphocytic choriomeningitis virus killer T cells are lethal only in weakly disseminated murine infections. J Exp Med. 1982 Jul 1;156(1):79–89. doi: 10.1084/jem.156.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. SJOGREN H. O., RINGERTZ N. Histopathology and transplantability of polyoma-induced tumors in strain A/Sn and three coisogenic resistant (IR) substrains. J Natl Cancer Inst. 1962 Apr;28:859–895. [PubMed] [Google Scholar]
  17. Serjeantson S. W. HLA and susceptibility to leprosy. Immunol Rev. 1983;70:89–112. doi: 10.1111/j.1600-065x.1983.tb00711.x. [DOI] [PubMed] [Google Scholar]
  18. Southern P., Oldstone M. B. Medical consequences of persistent viral infection. N Engl J Med. 1986 Feb 6;314(6):359–367. doi: 10.1056/NEJM198602063140606. [DOI] [PubMed] [Google Scholar]
  19. Splitter G. A., Eskra L., Abruzzini A. F. Cloned bovine cytolytic T cells recognize bovine herpes virus-1 in a genetically restricted, antigen-specific manner. Immunology. 1988 Jan;63(1):145–150. [PMC free article] [PubMed] [Google Scholar]
  20. Todd J. A., Acha-Orbea H., Bell J. I., Chao N., Fronek Z., Jacob C. O., McDermott M., Sinha A. A., Timmerman L., Steinman L. A molecular basis for MHC class II--associated autoimmunity. Science. 1988 May 20;240(4855):1003–1009. doi: 10.1126/science.3368786. [DOI] [PubMed] [Google Scholar]
  21. Townsend A. R., McMichael A. J. Specificity of cytotoxic T lymphocytes stimulated with influenza virus. Studies in mice and humans. Prog Allergy. 1985;36:10–43. doi: 10.1159/000409860. [DOI] [PubMed] [Google Scholar]
  22. Vladutiu A. O., Rose N. R. Autoimmune murine thyroiditis relation to histocompatibility (H-2) type. Science. 1971 Dec 10;174(4014):1137–1139. doi: 10.1126/science.174.4014.1137. [DOI] [PubMed] [Google Scholar]
  23. Whitton J. L., Gebhard J. R., Lewicki H., Tishon A., Oldstone M. B. Molecular definition of a major cytotoxic T-lymphocyte epitope in the glycoprotein of lymphocytic choriomeningitis virus. J Virol. 1988 Mar;62(3):687–695. doi: 10.1128/jvi.62.3.687-695.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zinkernagel R. M. Associations between major histocompatibility antigens and susceptibility to disease. Annu Rev Microbiol. 1979;33:201–213. doi: 10.1146/annurev.mi.33.100179.001221. [DOI] [PubMed] [Google Scholar]
  25. Zinkernagel R. M., Haenseler E., Leist T., Cerny A., Hengartner H., Althage A. T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay? J Exp Med. 1986 Oct 1;164(4):1075–1092. doi: 10.1084/jem.164.4.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zinkernagel R. M., Leist T., Hengartner H., Althage A. Susceptibility to lymphocytic choriomeningitis virus isolates correlates directly with early and high cytotoxic T cell activity, as well as with footpad swelling reaction, and all three are regulated by H-2D. J Exp Med. 1985 Dec 1;162(6):2125–2141. doi: 10.1084/jem.162.6.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zinkernagel R. M., Pfau C. J., Hengartner H., Althage A. Susceptibility to murine lymphocytic choriomeningitis maps to class I MHC genes--a model for MHC/disease associations. 1985 Aug 29-Sep 4Nature. 316(6031):814–817. doi: 10.1038/316814a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES