title: Intact proteins can bind to class II histocompatibility molecules with high affinity.
abstract: The ability of intact protein antigens to bind to purified class II histocompatibility molecules was investigated. Intact bovine ribonuclease (RNase) inhibited peptide binding to DR1 with a potency similar to that of a high affinity peptide or irreversibly denatured RNase. Similarly, horse myoglobin (Mb) was a potent inhibitor of peptide binding to I-E(k). I-E(k)-Mb complexes were directly visualized as a distinct band with reduced mobility on SDS PAGE. Direct binding experiments with biotin-labeled proteins demonstrated that Mb and RNase bind to class II molecules through the peptide-binding groove with high affinity, and that binding occurs in the absence of detergent. The possibility that HLA-DM can catalyse the binding of intact protein antigens was supported by the observation that DM enhances the binding of biotin-RNase to DR1. Our results provide further support for the hypothesis that intact, partially unfolded protein antigens can act as ligands for initial interaction with class II molecules.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, U.S.A.
authors.forename: H A
authors.initials: HA
authors.lastname: Runnels
authors.forename: D A
authors.initials: DA
authors.lastname: Weber
authors.forename: J C
authors.initials: JC
authors.lastname: Moore
authors.forename: L E
authors.initials: LE
authors.lastname: Westerman
authors.forename: P E
authors.initials: PE
authors.lastname: Jensen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001665:Binding Sites; D002417:Cattle; D003902:Detergents; D006183:H-2 Antigens / Q000378:metabolism*; D006681:HLA-D Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006736:Horses; D006801:Humans; D008024:Ligands; D009211:Myoglobin / Q000378:metabolism; D010047:Ovalbumin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012260:Ribonucleases / Q000378:metabolism
chemical_list: D003902:Detergents; D006183:H-2 Antigens; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D009211:Myoglobin; D010446:Peptide Fragments; D010047:Ovalbumin; D012260:Ribonucleases