The structure of songbird MHC class I reveals antigen binding that is flexible at the N-terminus and static at the C-terminus

Long-distance migratory animals such as birds and bats have evolved to withstand selection imposed by pathogens across the globe, pathogen richness is known be particularly high in tropical regions. Immune genes, so-called Major Histocompatibility Complex (MHC) are highly duplicated songbirds compared other vertebrates, this MHC diversity has been hypothesised result a unique adaptive immunity. To understand rationale behind evolution of genetic songbirds, we determined structural properties an class I protein, Acar3, from long-distance songbird, great reed warbler Acrocephalus arundinaceus (in short: Acar ). The structure Acar3 was studied complex with pathogen-derived antigens shows overall antigen presentation similar human I. However, peptides bound display unusual conformation: Whereas N-terminal ends enhanced flexibility, conformation their C-terminal halves rather static. This uncommon peptide-binding mode facilitated central Arg residue within groove that fixes backbone peptide at its position, potentially permits successful interactions between innate immune receptors. Our study highlights importance investigating system wild animals, bats, uncover mechanisms which may neither exist humans nor model organisms.