Definition of an extended MHC class II-peptide binding motif for the autoimmune disease-associated Lewis rat RT1.BL molecule.
The Lewis rat, an inbred rat strain susceptible to several well-characterized experimental autoimmune diseases, provides a good model to study 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 peptides. In the Lewis rat most autoimmune-associated CD4+ T cell responses are MHC class II RT1.BL restricted. In this study, the characteristics of RT1.BL-peptide interactions were explored. A series of substitution analogs of two Lewis rat T cell epitopes was examined in a direct peptide-MHC binding assay on isolated RT1.BL molecules. Furthermore, other autoimmune-related as well as non-disease-related T cell epitopes were tested in the binding assay. This has led to the definition of an extended RT1.BL-peptide binding motif. The RT1.BL-peptide binding motif established in this study is the first described rat MHC-peptide binding motif based on direct MHC-peptide binding experiments. To predict good or intermediate RT1.BL binding peptides, T cell epitope 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 rats.
Wauben
M H
MH
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
van der Kraan
M
M
Grosfeld-Stulemeyer
M C
MC
Joosten
I
I
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins; D001665:Binding Sites / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000502:physiology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016415:Sequence Alignment
D001426:Bacterial Proteins; D018834:Chaperonin 60; D018984:Epitopes, T-Lymphocyte; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides; C074119:heat-shock protein 65, Mycobacterium; C038353:histocompatibility antigens RT, rat; D018833:Chaperonins