CELLULAR IMMUNOLOGY 122,365-376 (1989) Class I Gene Regulation of Haplotype Preference May Influence Antiviral Immunity in Vivo ALLAN RANDRUP THOMSEN AND OLE MARKER Institute of Medical Microbiology, University of Copenhagen, Copenhagen, Denmark Received February 17, 1989; accepted April 25, I989 The lymphocytic choriomeningitis virus (LCMV)-specific Tc responsein (C3XD2) F, hybrids (kxd) is markedly biased in favor of the H-2d haplotype. Adoptive transfer experiments estab- lished 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, mater- nal 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 responseof(CXC3) F, and (C-H-2 dm2XC3) F, hybrids revealed that the domi- nance 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 responsedid 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 (CXC3) F, mice expressed an earlier and stronger virus-specific delayed type hypersensitivity responseand exerted a more efficient virus control than did (C-H-2dm2XC3) F, . Taken together these findings suggest that haplotype prefer- ence reflects a selection processfavoring the restriction element associatedwith the most efficient immune response in vivo. The implications of this are discussed. o 1989 Academic POW,, ILK. INTRODUCTION The understanding of the mechanisms determining whether a virus is cleared by the infected host is a subject of considerable interest. A variety of viruses have the ability to cause prolonged or persistent infections in humans and this may be associ- ated with considerable impairment of health ( 1). Thus, chronic hepatitis B virus infec- tion constitutes a major health problem (2) and the recent HIV epidemic is another example of what may happen if the host is unable to control a virus infection. The murine lymphocytic choriomeningitis virus (LCMV) infection has served as a model for studying the interplay between virus and immune system for many years, and results from this model have helped in the understanding of basic immunological problems like the restriction of T cell activity by the major histocompatibility com- plex (MHC) (3). Recently it has been demonstrated that the outcome of LCMV infec- tion in adult, immunocompetent animals is crucially affected by virus isolate as well asby the genetic makeup of the host (4-8). With regard to the latter both genesinside and outside the MHC region are important (5, 6, 8). Recently we have found that BALB/c mice are T cell high responders to Traub strain LCMV and control the infec- tion very efficiently, whereas H-2 identical DBA/2 are low responders and clear the virus much slower (7, 8). C3H mice were found to be intermediate in their ability to 365 0008-8749/89 $3.00 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.