Consequences of a single Ir-gene defect for the pathogenesis of lymphocytic choriomeningitis.
The H-2Ld allele has been identified by others as the sole Ir gene in the H-2d haplotype for the cytotoxic T lymphocyte (CTL) response to mouse lymphocytic choriomeningitis virus (LCMV). The BALB/c-H-2dm2 (C-H-2dm2) mutant lacks H-2Ld, and thus should be ideal for assessing the contribution of virus-immune CTL to LCM immunopathology. Comparison of the C-H-2dm2 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-2Ld did not prevent the later development of fatal disease in mice injected intracerebrally (i.c.) 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-2dm2, or (CBA X C-H-2dm2)F1 target cells. However, immune lymphocytes from both the mutant and the F1 strains lyse virus-infected BALB/c cells. Furthermore, B10.HTG and, in some experiments, B10.A(5R) mice generated CTL lytic for LCMV-infected BALB/c, C-H-2dm2, and (CBA X C-H-2dm2)F1 macrophages. Apparently H-2Ld is immunodominant in the H-2d-restricted response to LCMV. However, in the absence of H-2Ld, it seems that H-2Kd and, to a lesser extent, H-2Dd 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.
D000483:Alleles; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D005814:Genes, Viral; D006183:H-2 Antigens / Q000235:genetics*; D007668:Kidney; D008216:Lymphocytic Choriomeningitis / Q000235:genetics* / Q000382:microbiology; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity*; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens