THE PEPTIDE BINDING-SPECIFICITY OF THE MHC CLASS-II I-A MOLECULE OF THE LEWIS RAT, RT1.B

The specificity of peptide binding to MHC molecules is defined by bind ing motifs composed of several relatively conserved anchor positions. The peptide binding motifs of murine MHC class II I-A molecules are fu nctionally important but poorly characterized, Here we use peptide bin ding studies and isolation of naturally presented peptides to characte rize the peptide binding motif of the MHC class II I-A molecule, RT1.B -I, a molecule that is involved in experimental autoimmunity in the Le wis rat, We now report that, similar to other class II motifs, the RT1 .B-I motif consists of a nonamer sequence with four major anchor posit ions (P1, P4, P6 and P9), Residues at P4 and P9, rather than at pi, ap peared to be particularly important for binding, Negatively charged re sidues were favored at P9, consistent with the presence of a serine at position 57 of the RT1.B-I beta chain, This RT1.B-I motif could be ob served in the dominant autoantigenic T cell epitopes mapped previously in the Lewis rat, These results highlight a general similarity and so me important differences in the organization of MHC class II peptide b inding motifs, The reported RT1.B-I motif should facilitate the predic tion and design of T cell epitopes for the induction and control of ex perimental autoimmune diseases in Lewis rat models.