Genet. Sel. Evol.
Volume 35, Number Suppl. 1, 2003Second International Symposium on Candidate Genes for Animal Health
|Page(s)||S51 - S65|
Biological effect of varying peptide binding affinity to the BoLA-DRB3*2703 alleleZahra Alizadeha, Niel Karrowb and Bonnie A. Mallarda
a Ontario Veterinary College, Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada
b Animal and Poultry Science, Center for Genetic Improvement of Livestock, University of Guelph, Guelph, Ontario, Canada
(Accepted 26 February 2003)
MHC class I and II molecules are immunoregulatory cell surface glycoproteins, which selectively bind to and present antigenic peptides to T-lymphocytes. Murine and human studies show that variable peptide binding affinity to MHC II molecules influences Th1/Th2 responses by inducing distinctive cytokine expression. To examine the biological effects of peptide binding affinity to bovine MHC (BoLA), various self peptides (BoLA-DQ and fibrinogen fragments) and non-self peptides from ovalbumin (OVA), as well as VP2 and VP4 peptides from foot and mouth disease virus (FMD-V) were used to (1) determine binding affinities to the BoLA-DRB3*2703 allele, previously associated with mastitis susceptibility and (2) determine whether peptide binding affinity influences T-lymphocyte function. Peptide binding affinity was determined by a competitive assay using high affinity biotinylated self-peptide incubated with purified BoLA-DRB3*2703 in the presence of various concentrations of competing peptides. The concentrations of non-self peptide required to inhibit self-peptide binding by 50% (IC50) were variable, ranging from 26.92 to > 320 M. Peptide-specific T-lymphocyte function was determined by measuring DNA synthesis, cell division, and IFN- production in cultures of mononuclear cells from a BoLA-DRB3*2703 homozygous cow. When compared to non-stimulated control cultures, differences in lymphocyte function were observed for all of the assessed parameters; however, peptide-binding affinity did not always account for the observed differences in lymphocyte function.
Key words: bovine / MHC class II / peptide binding affinity / lymphocyte function
Correspondence and reprints: Niel Karrow
© INRA, EDP Sciences 2003