A major histocompatibility complex (MHC) class II molecule that binds the same viral pathogen peptide with both...

Classical molecules encoded by the major histocompatibility complex (MHC) are central to immune responses. Compared to typical mammals, the chicken MHC is small and simple, determining life or death from economically important pathogens like avian influenza virus and Marek's disease virus (MDV). Several genes within the tightly linked chicken MHC have been suggested to determine resistance and susceptibility to MDV, but it was a surprise to find that the dominantly expressed class II molecule from the resistant B2 haplotype employed a novel peptide-binding mode with a decamer core sequence compared to the susceptible B19 haplotype with a typical nonamer core. We examined the crystal structure of the dominantly expressed class II molecule from another resistant haplotype, B21, which is extremely frequent in commercial chicken flocks, to find that it bound the same MDV peptide with both nonamer and decamer cores, revealing an unexpected plasticity of binding that potentially increases the immune response to this devastating pathogen.IMPORTANCEThe meat and eggs of chickens are major food sources for both developed countries (where vast numbers are produced by the commercial poultry industry) and developing countries (where backyard and village chickens provide animal protein for the poorest members of society). Chickens are beset by many devastating viral diseases, and decades of genetics research has shown the particular haplotype of the major histocompatibility complex (MHC) can determine life or death for an individual chicken. One major economically important virus is the oncogenic herpesvirus that causes Marek's disease virus (MDV). Through structural studies, we find that the dominantly expressed class II molecule from an MHC haplotype that confers decisive resistance to MDV (and a number of other viruses) binds the same MDV peptide in two conformations, thus providing the basis for a wider immune response by T cells, which is of potential importance for both disease resistance and vaccine response.