The importance of MHC for Rous sarcoma virus and Marek's disease virus—Some Payne‐ful considerations

Abstract

In contrast to mammals, there are several viral diseases for which resistance and susceptibility are determined by particular chicken MHC haplotypes. At least one reason for this is that mammals express a multigene family of class I molecules, while common chicken haplotypes express only one class I molecule at high levels. We have determined the peptide‐binding motifs for the some dominantly‐expressed chicken class I molecules and found that they can explain the outcome of infections with the classic transforming retrovirus, Rous sarcoma virus (RSV). We have also found that the level of cell‐surface expression of chicken class I molecules varies between MHC haplotypes, and that this correlates inversely with the MHC‐determined resistance reported for classical Marek's disease virus (MDV). In this paper we consider two difficulties with these explanations. First, we examine the question of why the response to RSV depends on the MHC haplotype while the response to avian leukosis viruses (ALVs) does not. It would appear that the v‐src gene present in RSV but not ALVs is responsible, and we find that, of three peptides derived from the v‐src protein that bind the class I molecule of the resistant line CB, two differ quite significantly in sequence from the normal c‐src protein sequence. Second, we examine the issue of resistance and susceptibility to MDV due to genes outside of the 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 chromosome I that determines resistance and susceptibility to MDV may be the natural killer (NK) locus in an attractive perspective.