An insulin peptide that binds an alternative site in class II major histocompatibility complex.
We report that a peptide from the B chain of insulin, B(10-30), binds with high affinity to multiple class II proteins, including IAb,d,k, IEd,k, and DR1. The ability of B(10-30) to inhibit the binding of other peptide antigens to class II does not correlate with its affinity for class II. B(10-30) only weakly inhibits the binding of antigenic peptides. Conversely, peptides with high affinity for the peptide-binding groove of various class II proteins do not inhibit B(10-30) binding. The rate of association of B(10-30) with class II is unusually rapid, approaching saturation in 1-2 h compared with 1-2 d for classical peptide antigens in the same conditions. The dissociation rate is also relatively rapid. The B(10-30) peptide inhibits the binding of the super-antigen staphylococcal enterotoxin B (SEB) to IAk. It also inhibits SEB-mediated T cell activation. These observations support the conclusion that B(10-30) binds to a site outside the peptide-binding groove. Our findings indicate that short-lived peptide-class II complexes can be formed through interactions involving the SEB-binding site and raise the possibility that alternative complexes may serve as T cell receptor ligands.
Tompkins
S M
SM
Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
Moore
J C
JC
Jensen
P E
PE
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D004768:Enterotoxins / Q000633:toxicity; D015798:HLA-DR1 Antigen / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D013211:Staphylococcus aureus; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D004768:Enterotoxins; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007328:Insulin; D046911:Macromolecular Substances; D010446:Peptide Fragments; C031818:enterotoxin B, staphylococcal