Biological effect of varying peptide binding affinity to the BoLA-DRB3*2703 allele

Zahra Alizadeh; Niel Karrow; Bonnie A. Mallard

doi:doi:10.1051/gse:2003016

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Volume 35 / No Suppl. 1 (2003)

Genet. Sel. Evol., 35 Suppl. 1 (2003) S51-S65

Abstract

Free Access

Issue		Genet. Sel. Evol. Volume 35, Number Suppl. 1, 2003 Second International Symposium on Candidate Genes for Animal Health


Page(s)		S51 - S65
DOI		https://doi.org/10.1051/gse:2003016

Genet. Sel. Evol. 35 (2003) S51-S65
DOI: 10.1051/gse:2003016

Biological effect of varying peptide binding affinity to the BoLA-DRB32703* allele

Zahra Alizadeh^a, Niel Karrow^b and Bonnie A. Mallard^a

^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)

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 $\mu$ M. Peptide-specific T-lymphocyte function was determined by measuring DNA synthesis, cell division, and IFN- $\gamma$ 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