Crystal Structure of a Classical MHC Class I Molecule in Dogs; Comparison of DLA-88*0 and DLA-88*5 Category Molecules

Abstract

DLA-88 is a classical major histocompatibility complex (MHC) class I gene in dogs, and allelic DLA-88 molecules have been divided into two categories named “DLA-88*0” and “DLA-88*5.” The defining difference between the two categories concerns an LQW motif in the α2 domain helical region of the DLA-88*5 molecules that includes the insertion of an extra amino acid compared to MHC class I consensus length. We here show that this motif has been exchanged by recombination between different DLA-88 evolutionary lineages. Previously, with pDLA-88*508:01, the structure of a molecule of the DLA-88*5 category was elucidated. The present study is the first to elucidate a structure, using X-ray crystallography, of the DLA-88*0 category, namely DLA-88*001:04 complexed with β2m and a nonamer peptide derived from canine distemper virus (CDV). The LQW motif that distinguishes DLA-88*5 from DLA-88*0 causes a shallower peptide binding groove (PBG) and a leucine exposed at the top of the α2 domain helix expected to affect T cell selection. Peptide ligand amino acid substitution and pMHC-I complex formation and stability analyses revealed that P2 and P3 are the major anchor residue positions for binding to DLA-88*001:04. We speculate that the distribution pattern of the LQW motif among canine classical MHC class I alleles represents a strategy to enhance allogeneic rejection by T cells of transmissible cancers such as canine transmissible venereal tumor (CTVT).

Immunoinformatics for Novel Multi-Epitope Vaccine Development in Canine Parvovirus Infections

“…Tertiary structures of the chosen epitopes were determined utilizing the PEP-FOLD 3.5 server (accessed on 27 January 2022) [ 45 ] via docking with the DLA alleles DLA-88*001:04 (PDB ID: 7CJQ) [ 46 ] and DLA-88*50801 (PDB ID: 5F1I) [ 46 , 47 ], as suggested in previous articles [ 48 , 49 ]. Docking was performed using the PatchDock server (accessed on 29 January 2022) to ensure the binding of epitopes with DLA [ 50 ].…”