My research involves experimentally testing one of the theories on why the Major Histocompatibility Complex (MHC) is so diverse in mice. This theory is overdominant selection or heterozygous advantage. It states that MHC heterozygotes will have an advantage over homozygotes during coinfection. There are two ways this can happen: (1) if heterozygotes present more antigens or (2) if resistance is dominant, heterozygotes will express both resistant alleles. Possibility (1) is probably not happening since if this were true, then heterozygotes would have an advantage over homozygotes under any kind of infection, and this is not seen. Therefore, I am testing possibility (2) by infecting MHC congenic strains of mice with pathogens that show reciprocal resistance/susceptibility profiles. This means that MHC allele A is resistant to pathogen #1, but susceptible to pathogen #2, while MHC allele B is susceptible to pathogen #1 and resistant to pathogen #2. These pathogens are a temperature-sensitive mutant of Salmonella typhimurium (C5TS) and Theiler's Virus (TMEV).
With C5TS, MHC congenic strains BB and DD are susceptible while QQ is resistant. With TMEV, MHC congenic strains BB and DD are resistant while QQ is susceptible. I bred the heterozygotes, BQ and DQ and infected them and the homozygotes with both pathogens and each pathogen alone as controls.
With both MHC heterozygote strains tested, BQ and DQ, I find that heterozygotes do have an advantage in the F2 generation. However, the F1 weight data seems to indicate that the F1 mice are enjoying heterosis. If this is true (testing presently), then it will change the way immunologists use congenic strains of mice.
Test different haplotypes of MHC congenic mice with the same pathogens to see if heterozygotes only have an advantage when the pathogens exhibit reciprocal resistance/susceptibility profiles.
Also, do serial passage experiments with Theiler's Virus in heterozygotes to see if pathogens find it harder to escape the immune system of heterozygotes.