Class-I Gene-Regulation Of Haplotype Preference May Influence Antiviral Immunity Invivo

The lymphocytic choriomeningitis virus (LCMV)-specific Tc response in (C3×D2) F 1 hybrids (k×d) is markedly biased in favor of the H-2 d 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×C3) F 1 and (C-H-2 dm2 ×C3) F 1 hybrids revealed that the dominance of the H-2 d haplotype was controlled by H-2L d . The ability of this gene to down-regulate the generation of an H-2 k -restricted response did not seem to reflect antigenic mimicry since H-2 k -restricted LCMV-specific Tc did not lyse H-2 d expressing targets. In regard to the in vivo significance of haplotype preference it was found that (C×C3) f 1 mice expressed an earlier and stronger virus-specific delayed type hypersensitivity response and exerted a more efficient virus control than did (C-H-2 dm2 ×C3) f 1 . 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.