Crystal structure of the giant panda MHC class I complex: first insights into the viral peptide presentation profile in the bear family

The viral cytotoxic T lymphocyte (CTL) epitope peptides presented by classical MHC-I molecules require the assembly of a peptide-MHC-I-β2m (aka pMHC-I) trimolecular complex for TCR recognition, which is the critical activation link for triggering antiviral T cell immunity. Ursidae includes 5 genera and 8 species; however, research on T cell immunology in this family, especially structural immunology, is lacking. In this study, the structure of the key trimolecular complex pMHC-1 (aka pAime-128), which binds a peptide from canine distemper virus, was solved for the first time using giant panda as a representative species of Ursidae. The structural characteristics of the giant panda pMHC-I complex, including the unique pockets in the peptide-binding groove (PBG), were analyzed in detail. Comparing the panda pMHC-I to others in the bear family and extending the comparison to other mammals revealed distinct features. The interaction between MHC-I and β2m, the features of pAime-128 involved in TCR docking and CD8 binding, the anchor sites in the PBG, and the CTL epitopes of potential viruses that infect pandas were concretely clarified. Unique features of pMHC-I viral antigen presentation in the panda were revealed by solving the three-dimensional structure of pAime-128. The distinct characteristics of pAime-128 indicate an unusual event that emerged during the evolution of the MHC system in the bear family. These results provide a new platform for research on panda CTL immunity and the design of vaccines for application in the bear family.