Characterization of the ovine Major Histocompatibility Complex (MHC) class I genes

• Main Author: Miltiadou, Despoin
• Published: University of Edinburgh 2006
• Subjects: 636.089
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.657835

To develop cellular and molecular tools to support development of vaccines against intracellular pathogens of sheep, a molecular genetic analysis of four distinct ovine MHC haplotypes carried by two heterozygous Blackface rams (501 and 504) was conducted. A total of 17 novel sequences was identified, 11 of which were obtained full length. Phylogenetic analysis using the identified transcripts and published ovine, bovine and other ruminant class I sequences belonging to the <i>Bovidae</i> family indicated that there are at least six ovine MHC class I loci (chapter 6). Sequence N1 and N2 are closer to the non classical bovine MHC class I sequence HD15 than to the remaining ovine class I transcripts. Seven out of eight full length transcripts subcloned into a mammalian expression vector expressed detectable class I cell surface glycoproteins in COS-7 cells (chapter 7). The combination of phylogenetic analysis, haplotype, transcription and expression data suggest that there are at least four distinct polymorphic ovine MHC class I loci, three of which appear to be expressed in a number of combinations in individual haplotypes, a couple of non polymorphic poorly transcribed class I like sequences and at least one additional diverged non classical class I locus (chapter 8). Similarities and differences of the ovine MHC class I region with that of other species and implications in immune response and sustainable control of intracellular sheep pathogens are discussed. Using the data generated here, an MHC defined sheep flock, which includes animals homozygous for each of the four MHC haplotypes, is currently under development. The MHC defined resource population, along with the transfected cell lines expressing each of the full length ovine MHC class I sequences, comprise tools for immunization and disease association experiments studying the protective immunity to intracellular pathogens of sheep.