Impact of MHC Class I Gene on Resistance to Murine AIDS

Abstract

Development of murine AIDS in mice following infection with LP-BM5 murine leukaemia virus (MuLV) is highly strain dependent, with strain differences determined by genes within and outside H-2. Among H-2 genes, the Dd gene is the most closely associated with resistance to LP-BM5 MuLV infection. However, the Dd-mediated resistance is highly influenced by outside H-2 genes, i.e. A lineage strains are more resistant than mice strains of B6/B10 lineage. In this study, the mice having BALB background were analysed and, similarly to A lineage mice, only Dd gene products were found to be required to provide resistance to LP-BM5 MuLV infection. Furthermore, BALB/c Kh mice bearing both Dd and Ld genes clearly showed obviously higher resistance than BALB/c-H-2dm2 mice solely having the Dd gene. In addition, in the long-term observation of the effect of the Dd gene on B6/B10 background mice, D8 mice having the Dd gene as a transgene and expressing a high level Dd gene product showed higher resistance than naturally recombinant B10.A(18R) mice. These results suggest that the MAIDS resistance associated with the D end loci is dependent on the level of expression of an MHC class I gene.

Control of immunodeficiency and lymphoproliferation in mouse AIDS: studies of mice deficient in CD8+ T cells or perforin

“…Strain differences in response to this infection are genetically determined, with genes of the major histocompatibility complex (MHC) having, in many circumstances, the major influence on susceptibility to MAIDS. Within the MHC, class I genes at the D end are most clearly associated with resistance to MAIDS (21,22), but modulating effects of class II genes, both I-A and I-E, are well documented (23). Genes outside of the MHC can also critically affect the development of disease (20,21).…”