THE MINIMAL ESSENTIAL MHC REVISITED - BOTH PEPTIDE-BINDING AND CELL-SURFACE EXPRESSION LEVEL OF MHC MOLECULES ARE POLYMORPHISMS SELECTED BYPATHOGENS IN CHICKENS

Birds, like mammals, have a highly polymorphic MHC that determines str ong allograft rejection. However, in contrast to mammals, there are a number of viral diseases for which resistance and susceptibility are d etermined by particular chicken MHC haplotypes. We have found that cer tain common chicken MHC haplotypes express only one class I molecule a t 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 resi stance of the chicken B21 haplotype to classical Marek's disease virus , a relatively large pathogen for which any MHC molecule should find p eptides. In 40 chicken lines, the level of class I expression correlat es with the level of MHC-determined susceptibility to Marek's disease, the most susceptible B19 with the highest expression and the most res istant B21 with the lowest expression. Thus, cell surface expression l evel of class I molecules appears to be a polymorphism under selection by infectious pathogens, just like peptide-binding specificity. We sp eculate that these expression level differences are another manifestat ion of the simple MHC of chickens, which in human and mouse haplotypes are averaged out.