Issue |
Genet. Sel. Evol.
Volume 35, Number Suppl. 1, 2003
Second International Symposium on Candidate Genes for Animal Health
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|
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Page(s) | S51 - S65 | |
DOI | https://doi.org/10.1051/gse:2003016 |
DOI: 10.1051/gse:2003016
Biological effect of varying peptide binding affinity to the BoLA-DRB3*2703 allele
Zahra Alizadeha, Niel Karrowb and Bonnie A. Mallardaa 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)
Abstract
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
e-mail: nkarrow@uoguelph.ca
© INRA, EDP Sciences 2003