Cattle MHC: evolution in action?

Because major histocompatibility complex (MHC) genes play a major role in t he development of acquired immune responses, it is essential to obtain comp arative information on their organisation, expression and possible function al dichotomies in different species. In human, three classical, polymorphic class I genes (HLA-A, B- and -C) and four expressed A/B class II gene pair s (HLA-DM, -DP, -DQ and -DR) are each present on all haplotypes. With the e xception of the HLA-DRB loci, it has been assumed that a similar rigid orga nisational situation exists in other mammalian species. However, extensive analysis of the bovine MHC (BoLA) at both the genomic and transcriptional l evels has revealed a degree of genetic fluidity not described in other spec ies. None of the four (or more) classical class I genes identified is consi stently expressed, and haplotypes differ from one another in both the numbe r and composition of expressed class I genes. Similarly, in the class II re gion, the number of DQ genes varies between haplotypes in both number and c omposition. These variations in both class I and II (which appear to reflec t differences at the genomic level) are Likely to play an important role in cattle immune responses. The observed phenotypic differences in cattle dem onstrate very clearly the dynamic nature of the MHC region. This review add resses the functional impact of such variation in different breeds and popu lations, and its significance in terms of MHC evolution.