Crystal structure of the classical MHC-I molecule: insights into the MHC-I system in antiviral diseases in dogs

Abstract

AbstractOnly one classical MHC-I locus (aka DLA-88) evolved in dogs, and thus far, a total of 76 DLA-88 alleles can be divided into two categories. The first category consists of 60 alleles, and the second category consists of 16 alleles. The main difference between the two categories is the insertion of an amino acid in the α2 region of DLA-88 alleles. To elucidate the structure of the first category, in this study, the crystal structure of pDLA-88*001:01 was determined for the first time. The 3D structure and topological characteristics of the ABG of pDLA-88*001:01 with a CDV peptide were analyzed. The viral presentation profile and the binding motif of viruses presented by pDLA-88*001:01 were determined. Most importantly, there were no amino acid insertions in the α2 region of the first category, which changed the conformation of the D pocket and the docking of the TCR. The results suggest obvious differences between the two categories. Because of the variation in the α2 region, pDLA-88*001:01 showed distinctive features in the two categories. Due to the peptide-binding motif of pDLA-88*001:01, more than 320 high-affinity viral peptides were predicted from dog H7N9, CPV, CMV, CMV, and CDV strains. The results reveal that there are two kinds of structural MHC-I systems in dogs that are responsible for CTL immunity against viral diseases. The results provide knowledge for designing viral epitope vaccines in canines.ImportanceDLA plays an important role in the acquired immunity of organism. In previous study, the pMHC-I structure of dog was analyzed with DLA-88 self-peptide. In this study, we screened several viral peptides which can bind to DLA-88 and resolved the structure of the DLA-88 complex binding the CDV peptide. This study enriches the study of canine MHC-I molecular-presenting polypeptide-activated TCR, which is of great significance for the study of canine cellular immunity and anti-viral vaccine development.