2018 journal article

The canine MHC class Ia allele DLA-88*508:01 presents diverse self- and canine distemper virus-origin peptides of varying length that have a conserved binding motif

Veterinary Immunology and Immunopathology, 197, 76–86.

By: P. Ross n, P. Nemec n, A. Kapatos n, K. Miller*, J. Holmes n, S. Suter n, A. Buntzman*, E. Soderblom*, E. Collins*, P. Hess n

author keywords: Canine distemper virus; CD8(+) T lymphocytes; MHC; Peptides/Epitopes; Retrovirus
MeSH headings : Alleles; Amino Acid Motifs; Animals; Antigen Presentation; Distemper Virus, Canine / chemistry; Distemper Virus, Canine / immunology; Dogs / genetics; Epitopes / chemistry; Epitopes / immunology; Genes, MHC Class I; Histocompatibility Antigens Class I / genetics; Histocompatibility Antigens Class I / immunology; Peptides / chemistry; Peptides / immunology; Protein Binding; T-Lymphocytes / immunology; Viral Proteins / chemistry; Viral Proteins / immunology
TL;DR: The presentation of diverse self and viral peptides indicates that DLA-88 is a classical MHC class Ia gene, and thus, potential targets of anti-viral CTL in D LA-88*508:01-bearing dogs. (via Semantic Scholar)
Source: Crossref
Added: July 20, 2019

Ideally, CD8+ T-cell responses against virally infected or malignant cells are defined at the level of the specific peptide and restricting MHC class I element, a determination not yet made in the dog. To advance the discovery of canine CTL epitopes, we sought to determine whether a putative classical MHC class Ia gene, Dog Leukocyte Antigen (DLA)-88, presents peptides from a viral pathogen, canine distemper virus (CDV). To investigate this possibility, DLA-88*508:01, an allele prevalent in Golden Retrievers, was expressed as a FLAG-tagged construct in canine histiocytic cells to allow affinity purification of peptide-DLA-88 complexes and subsequent elution of bound peptides. Pattern analysis of self peptide sequences, which were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), permitted binding preferences to be inferred. DLA-88*508:01 binds peptides that are 9-to-12 amino acids in length, with a modest preference for 9- and 11-mers. Hydrophobic residues are favored at positions 2 and 3, as are K, R or F residues at the C-terminus. Testing motif-matched and -unmatched synthetic peptides via peptide-MHC surface stabilization assay using a DLA-88*508:01-transfected, TAP-deficient RMA-S line supported these conclusions. With CDV infection, 22 viral peptides ranging from 9-to-12 residues in length were identified in DLA-88*508:01 eluates by LC-MS/MS. Combined motif analysis and surface stabilization assay data suggested that 11 of these 22 peptides, derived from CDV hemagglutinin, large polymerase, matrix, nucleocapsid, and V proteins, were processed and presented, and thus, potential targets of anti-viral CTL in DLA-88*508:01-bearing dogs. The presentation of diverse self and viral peptides indicates that DLA-88 is a classical MHC class Ia gene.