Limited polymorphism in the first domain of the rat MHC class II RT1-D molecule

The rat is a widely used experimental animal, but the scanty knowledge concerning the structural major histocompatibility complex (MHC) class II polymorphism diminishes its use as a model for diseases mediated by the immune system. The MHC class II molecules are peptide receptors presenting restricted sets of peptides to T cells, and knowledge of the peptide binding domain structures of the MHC molecule is needed to understand peptide repertoire selection and presentation to T cells. Armed with such knowledge, researchers can investigate the molecular basis for diseases involving T-cell immunity. The high degree of polymorphism in the MHC class TI genes makes them valuable for evolutionary studies. The human classical class II HLA-DO is polymorphic in the genes for both the alpha and the beta chain. The other classical class II HLA-DQ locus is among the most polymorphic in the genome, whereas for the DRA locus, coding for the complementing class II chain, only two alleles have been reported. In addition, they differ only in the second domain. The mouse DRB homologue H2-Eb shows a high degree of polymorphism as well. In the mouse there also seems to be a selective pressure to limit polymorphism in this gene. Several haplotypes have no functional expression owing to defective RNA splicing or mutations in one or both of the H2-E genes (Dembic et al. 1955, Tacchini-Cottier and Jones 1988: Vu et al. 1989). All rat haplotypes investigated appear to have a functional D molecule (Butcher and Howard 1986).