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.