Class I gene regulation of haplotype preference may influence antiviral immunity in vivo.
The lymphocytic choriomeningitis virus (LCMV)-specific Tc response in (C3 X D2) F1 hybrids (k X d) is markedly biased in favor of the H-2d haplotype. Adoptive transfer experiments established that this haplotype preference also applied to T cell function in vivo. Using different mouse strain combinations we were unable to detect an influence of sex, non-H-2 background, maternal genotype, or route of priming on the preference pattern. In other haplotype combinations tested (k and b, b and d) no distinct haplotype preference was observed. A comparison of the LCMV-specific Tc response of (C X C3) F1 and (C-H-2dm2 X C3) F1 hybrids revealed that the dominance of the H-2d haplotype was controlled by H-2Ld. The ability of this gene to down-regulate the generation of an H-2k-restricted response did not seem to reflect antigenic mimicry since H-2k-restricted LCMV-specific Tc did not lyse H-2d expressing targets. In regard to the in vivo significance of haplotype preference it was found that (C X C3) F1 mice expressed an earlier and stronger virus-specific delayed type hypersensitivity response and exerted a more efficient virus control than did (C-H-2dm2 X C3) F1. Taken together these findings suggest that haplotype preference reflects a selection process favoring the restriction element associated with the most efficient immune response in vivo. The implications of this are discussed.
Thomsen
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AR
Institute of Medical Microbiology, University of Copenhagen, Denmark.
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D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice / Q000276:immunology*; D013154:Spleen / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D006183:H-2 Antigens