The "Minimal Essential MHC" revisited: Both peptide-binding and cell surface expression level of MHC molecules are polymorphisms selected by pathogens in chickens

Birds, like mammals, have a highly polymorphic MHC that determines strong allograft rejection. However, in contrast to mammals, there are a number of viral diseases for which resistance and susceptibility are determined by particular chicken MHC haplotypes. We have found that certain common chicken MHC haplotypes express only one class I molecule at high levels. The selection on a single MHC gene should be strong, in contrast to the situation in mammals. We have determined the peptide motifs for the dominant class I molecules from a number of chicken MHC haplotypes and found that they can explain the outcome of infections with a small virus. However, the strongest MHC association is the resistance of the chicken B21 haplotype to classical Marek's disease virus, a relatively large pathogen for which any MHC molecule should find peptides. In 40 chicken lines, the level of class I expression correlates with the level of MHC-determined susceptibility to Marek's disease, the most susceptible B19 with the highest expression and the most resistant B21 with the lowest expression. Thus, cell surface expression level of class I molecules appears to be a polymorphism under selection by infectious pathogens, just like peptide-binding specificity. We speculate that these expression level differences are another manifestation of the simple MHC of chickens, which in human and mouse haplotypes are averaged out.