Allelic variations in rat MHC class II binding of myelin basic protein peptides correlate with encephalitogenicity

The impact of the strength and promiscuity of the self peptide--MHC class i i interaction on susceptibility to autoimmune disease is uncertain. Here we studied allelic differences in the affinity of rat MHC class II molecules for myelin basic protein (MBP) peptides spanning from position 63 to 106. P redominantly peptides from this region are immunogenic: in the rat and the MHC class II region determines if the response is disease promoting or dise ase protective. Strikingly, RT1.B (DQ-like) molecules showed much more alle lic variation of MBP peptide binding than RT1.D (DR-like) molecules. Modera te to strong binding of particular MBP peptides correlated with their previ ously documented encephalitogenicity. Moreover, the differences in disease susceptibility to certain MBP peptides observed in the different rat strain s were? clearly reflected in the allelic diversity of the peptide binding p rofiles. In conclusion our findings demonstrate that disease-inducing stret ches of MBP generally comprise good binding peptides.