Canine MHC Genes Influence Immune Responses to Defined Peptide Epitopes
British Small Animal Veterinary Congress 2008
M. Hafskjold; B. Catchpole
Department of Pathology and Infectious Diseases, The Royal Veterinary College
North Mymms, Hatfield, Hertfordshire

Dog Leukocyte Antigen (DLA) genes encode Major Histocompatibility Complex (MHC) molecules that are responsible for presenting antigens to the immune system. Antigen is normally processed and peptide fragments (epitopes) presented in association with MHC Class II molecules for activation of CD4+ T helper cells, important for both cell- and antibody-mediated immunity. In the canine population, there is considerable inter-breed but often minimal intra-breed variability in DLA genes. The DLA genotype of each individual animal will dictate the peptide epitopes that can be recognised and therefore the T cell repertoire that responds to the antigen. This means that there will be differences comparing dogs of different breed in terms of their immune response to infection or vaccination. The aim of the current study was to investigate whether DLA genes influence immune responses when animals are exposed to defined peptide epitopes.

A total of 28 dogs of representative breeds (cocker spaniel, springer spaniel, GSD, labrador, setter, pointer and terrier) were immunised with synthetic peptides representing a known B cell epitope (peptide G4-10) linked to one of 7 T helper epitopes. Serum was taken 4 weeks after the final immunisation and tested for the presence of antibodies against the G4-10 peptide by enzyme-linked immunosorbent assay (ELISA). Genomic DNA was extracted from EDTA blood samples and each dog DLA-genotyped by sequence-based typing.

There was wide individual variation in serological responses to the G4-10 peptide, following immunisation. In general terms, DLA heterozygous dogs seemed to respond better than homozygous dogs. Cocker spaniels, particularly those that were homozygous for the DRB1*006; DQA1*005; DQB1*020 haplotype made the weakest response as a breed group, although one heterozygous cocker spaniel made a strong response. One GSD that was homozygous for DRB1*011; DQA1*002; DQB1*01302 made the weakest response compared to the other three heterozygous GSD. Two of the highest responder dogs (one labrador and one terrier) were heterozygous and shared the DRB1*008; DQA1*003; DQB1*004 haplotype. These results indicate that there are breed differences in immune responses to the same immunogen. Thus, the use of beagles for vaccine research does not necessarily predict immune responses in the wider dog population. It does appear that DLA genes play a role in determining the epitope repertoire that can be presented to the immune system.

Speaker Information
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M. Hafskjold
Department of Pathology and Infectious Diseases
The Royal Veterinary College
Hatfield, Hertfordshire, UK


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