Spontaneous autocytotoxicity against an unexpected H-2d haplotype in MRL/lpr (H-2k) autoimmune disease-prone mice.
The MRL/lpr (H-2k) inbred strain, a model for the autoimmune disease systemic lupus erythematosus, differs from the healthy inbred strain MRL +/+ (H-2k) by only 0.1% of its genome. Southern blot analysis using class I and class II probes confirmed the H-2k genotype of both strains. Among the Iak-positive peritoneal cells, cells with an unexpected expression of Iad specificities were detected in a radioimmunoassay using several monoclonal antibodies and one conventional antiserum. This was only found in aged (6- to 9-month-old) mice both in the MRL/lpr strain (32% Iad-positive mice) and in the MRL +/+ strain (42% Iad-positive mice). Furthermore, 24% of aged MRL/lpr mice exhibited strong spontaneous cytotoxic T lymphocyte (CTL) activities against P815 (H-2d) target cells, and 57% had a weaker but still detectable level of cytotoxicity. In contrast, such a CTL activity has never been found in the MRL +/+ strain. These results suggest that the anti-H-2d CTL plays a role in the onset of the autoimmune process in MRL/lpr mice.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D006183:H-2 Antigens