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The impact of the strength and promiscuity of the self peptide-MHC class II 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. Predominantly peptides from this region are immunogenic in the rat and the MHC class II region determines if the response is disease promoting or disease protective. Strikingly, RT1.B (DQ-like) molecules showed much more allelic variation of MBP peptide binding than RT1.D (DR-like) molecules. Moderate to strong binding of particular MBP peptides correlated with their previously documented encephalitogenicity. Moreover, the differences in disease susceptibility to certain MBP peptides observed in the different rat strains were clearly reflected in the allelic diversity of the peptide binding profiles. In conclusion our findings demonstrate that disease-inducing stretches of MBP generally comprise good binding peptides.

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