A Newly Recognized Pairing Mechanism of the α- and β-Chains of the Chicken Peptide–MHC Class II Complex

Abstract

MHC class II (MHC-II) molecules play a crucial role in cellular and humoral immunity by forming peptide-MHC-II (pMHC-II) complexes. The three-dimensional structures of pMHC-II complexes have been well resolved in humans and mice. However, there is no structural information for pMHC-II complexes in nonmammals. In chickens, there are two closely related and highly polymorphic β-chains and one monomorphic α-chain, and the mechanism by which one monomorphic α-chain combines with two polymorphic β-chains to form a functional heterodimer remains unknown. In this study, we report the crystal structure of a chicken pMHC-II complex (pBL2*019:01) at 1.9-Å resolution as the first nonmammalian structure of a pMHC-II complex. The structure reveals an increase in hydrogen bonding between the α and β main chains at the central interface that is introduced by the insertion of four residues in the α-chain. The residues in the β-chain that form hydrogen bonds with the α-chain are conserved among all β alleles. These structural characteristics explain the phenomenon of only one <i>BLA</i> allele without sequence variation pairing with highly diverse <i>BLB</i> alleles from two loci in the genome. Additionally, the characteristics of the peptide in the peptide-binding groove were confirmed. These results provide a new understanding of the pairing mechanism of the α- and β-chains in a pMHC-II complex and establish a structural principle to design epitope-related vaccines for the prevention of chicken diseases.