THE IMPORTANCE OF MHC FOR ROUS-SARCOMA VIRUS AND MAREKS-DISEASE-VIRUS- SOME PAYNE-FUL CONSIDERATIONS

In contrast to mammals, there are several viral diseases for which res istance and susceptibility are determined by particular chicken MHC ha plotypes, At least one reason for this is that mammals express a multi gene family of class I molecules, while common chicken haplotypes expr ess only one class I molecule at high levels. We have determined the p eptide-binding moths for the some dominantly-expressed chicken class I molecules and found that they can explain the outcome of infections w ith the classic transforming retrovirus, Rous sarcoma virus (RSV). We have also found that the level of cell-surface expression of chicken c lass I molecules varies between MHC haplotypes, and that this correlat es inversely with the MHC-determined resistance reported for classical Marek's disease virus (MDV), In this paper we consider two difficulti es with these explanations, First, we examine the question of why the response to RSV depends on the MHC haplotype while the response to avi an leukosis viruses (ALVs) does not, It would appear that the v-src ge ne present in RSV but not. ALVs is responsible, and we find that, of t hree peptides derived from the v-src protein that bind the class I mol ecule of the resistant line CB, two differ quite significantly in sequ ence from the normal c-src protein sequence, Second, we examine the is sue of resistance and susceptibility to MDV due to genes outside of th e MHC. It is possible that such genes interact with the class I genes in the MHC, which puts the recent observation that a gene on chicken c hromosome I that determines resistance and susceptibility to MDV may b e the natural killer (NK) locus in an attractive perspective.