Variations in immune response as determined by MHC class 1 polymorphism in cattle

Abstract

Major histocompatibility complex (MHC) class I molecules play an essential role in the defence against intracellular pathogens. CD8+ T cells recognise antigenic peptides in association with self-MHC, a process known as MHC restriction. In this study we examined bovine MHC class I genes using both molecular and cellular approaches. There is evidence for the existence of five or six classical class I loci in cattle, with the number of genes expressed varying between haplotypes. Most alleles are putatively assigned to a locus according to their grouping following phylogenetic analysis. Here we applied reference strand mediated conformational analysis (RSCA), a high resolution typing method, to four of these groups: 1, 2, 3 and 6. Using group-specific primers and two reference strands 22 potential new alleles were identified with one probable pseudoallele in group 1. Based on the results obtained and previous phylogenetic analysis, groups 1 and 3 appear to be the most polymorphic.The need for a reliable typing method for MHC class I genes in cattle can be seen through studies of CD8+ T cell responses to Theileria parva. T. parva is an intracellular parasite against which CD8+ CTL have been shown to be the principal effector cells in infected cattle. Previous studies identified a clear bias in class I restriction of CTL to either the maternal or paternal haplotype, and showed that haplotypes differ in their ability to restrict this response. We have extended these studies using animals with wellcharacterised haplotypes. We showed that the A14 and A18 haplotypes appear to be dominant over the A10 and A31 haplotypes respectively. A14 expresses three class I genes, D18.1, D18.4 and D18.5. Assays testing an A14-restricted CTL clone against D18.1 and D18.4 transfected target cells proved inconclusive indicating a need for further investigation and the inclusion of D 18.5 in any studies.