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.