DEFINITION OF AN EXTENDED MHC CLASS-II PEPTIDE BINDING MOTIF FOR THE AUTOIMMUNE DISEASE-ASSOCIATED LEWIS RAT RT1.B-L MOLECULE

The Lewis rat, an inbred rat strain susceptible to several well-charac terized experimental autoimmune diseases, provides a good model to stu dy peptide-mediated immunotherapy, Peptide immunotherapy focussing on the modulation of T cell responses by interfering with TCR-peptide-MHC complex formation requires the elucidation of the molecular basis of TCR-peptide-MHC interactions for an efficient design of modulatory pep tides. In the Lewis rat most autoimmune-associated CD4(+) T cell respo nses are MHC class II RT1.B-L restricted, In this study, the character istics of RT1.B-L-peptide interactions were explored, A series of subs titution analogs of two Lewis rat T cell epitopes was examined in a di rect peptide-MHC binding assay on isolated RT1.B-L molecules. Furtherm ore, other autoimmune-related as well as non-disease-related T cell ep itopes were tested in the binding assay, This has led to the definitio n of an extended RT1.B-L-peptide binding motif. The RT1.B-L-peptide bi nding motif established in this study is the first described rat MHC-p eptide binding motif based on direct MHC-peptide binding experiments. To predict good or intermediate RT1.B-L binding peptides, T cell epito pe search profiles were deduced from this motif. The motif and search profiles will greatly facilitate the prediction of modulatory peptides based on autoimmune-associated T cell epitopes and the identification of target structures in experimental autoimmune diseases in Lewis rat s.