Structural and functional diversity arising from intra- and inter-haplotype combinations of duplicated DQA and B loci within the ovine MHC

Abstract

In sheep, the A and B loci encoding the α and β chains of the classical class II MHC molecules are DRA and DRB and DQA and DQB. Previous analyses described the duplication of the DQA and DQB genes. The majority of haplotypes include DQA1 and DQA2 loci, however, in a number of haplotypes, DQA1 appears absent and these haplotypes have been described as DQA1 null. In these haplotypes, the DQA2 locus is found in combination with a second locus which appeared more closely related to DQA2 than DQA1, hence the description of this locus as DQA2-like. Here we combine our previous analysis of the DQA transcripts with an analysis of the associated DQB transcripts in ten haplotypes from MHC homozygous animals. This allows the potential for surface expression of different haplotype combinations of DQA and B genes and the functional significance of DQA2-like and its predicted DQB partner to be determined. Atypical DQB transcripts (DQB2-like) were identified in haplotypes classified as DQA1-null and conserved DQB2-like orthologues were identified in other Bovidae indicating trans-species conservation of the allelic lineage. Functional combinations detected by co-transfection of DQ1, DQ2 and DQ2-like genes demonstrates the potential for a wide range of DQ molecules derived from both intra- and inter-haplotype as well as inter-locus combinations. We provide evidence that DQA2-like and B2-like genes form an evolutionary conserved pair which generates structurally distinct class II molecules that are likely to present a distinct range of peptides to CD4+ T cells.