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) clas s 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 t he peptide binding domain structures of the MHC molecule is needed to understand peptide repertoire selection and presentation to T cells. A rmed with such knowledge, researchers can investigate the molecular ba sis for diseases involving T-cell immunity. The high degree of polymor phism in the MHC class TI genes makes them valuable for evolutionary s tudies. The human classical class II HLA-DO is polymorphic in the gene s 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 a lleles have been reported. In addition, they differ only in the second domain. The mouse DRB homologue H2-Eb shows a high degree of polymorp hism as well. In the mouse there also seems to be a selective pressure to limit polymorphism in this gene. Several haplotypes have no functi onal expression owing to defective RNA splicing or mutations in one or both of the H2-E genes (Dembic et al. 1955, Tacchini-Cottier and Jone s 1988: Vu et al. 1989). All rat haplotypes investigated appear to hav e a functional D molecule (Butcher and Howard 1986).