Pathogen variants that escape MHC-dependent immune recognition will be favored by natural selection. We are testing this prediction by conducting experimental evolution experiments involving serial passage of various pathogens through strains of mice that differ only at MHC genes. We know pathogens adapt during such passages as reflected in increased virulence. These experiments will determine if some of the increased virulence is MHC-dependent. We have also begun testing the heterozygote advantage hypothesis and have recently demonstrated that MHC heterozygotes have an advantage when coinfected with Salmonella and Theiler's virus.
Heterozygotes have no advantage when infected individually with either pathogen.
This is the first experimental confirmation that MHC heterozygote advantage may emerge because heterozygotes have greater overall resistance during multiple infections. We are investigating the adaptive significance and mechanisms of MHC-based mating preferences. We are using olfaction assays and cross-fostering experiments designed to reveal the development of odor profiles that individuals subsequently avoid during mate choice. MHC studies have largely been restricted to humans and laboratory rodents. To expand the breadth of questions that can be addressed, we are cloning and sequencing MHC genes in other vertebrate species.