Susceptibility to murine lymphocytic choriomeningitis maps to class I MHC genes—a model for MHC/disease associations

Abstract

Susceptibility to some human diseases is linked, albeit weakly, to major transplantation antigens (HLA) encoded by the major his-tocompatibility gene complex (MHC)^1,2. Here we have studied MHC/disease association in inbred strains of mice after intracere-bral (i.e.) injection of lymphocytic choriomeningitis virus (LCMV)^3–6. This route of infection leads to a lymphocytic choriomeningitis (LCM) which is not the result of direct cytopathic effects of the virus but is caused by the induced T-cell immune response: immunocompetent mice die whereas T-cell-deficient mice survive^3–6. By using two plaque variants of LCMV strain UBC (refs 7, 8), we found that susceptibility to LCM was dependent on the LCMV strain used (‘aggressive’ versus ‘docile’ UBC-LCMV) and on the various genes of the host mouse strains. In addition, susceptibility to LCM caused by docile UBC-LCMV was clearly linked to the murine maior histocompatibility locus H–2D: in MHC-congeneic C57BL/10 mice, susceptibility correlated with early onset and high activity of measurable LCMV-specific cytotoxic T cells in meninges and spleens and could be mapped to H–2D. This model shows that a severe immunopathologically mediated clinical disease in mice can be regulated directly by MHC genes of class I type and supports the notion that many MHC/disease associations directly reflect MHC-restricted and MHC-reguIated T-cell reactivity⁹.