Intact proteins can bind to class II histocompatibility molecules with high affinity.
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.
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H A
HA
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, U.S.A.
Weber
D A
DA
Moore
J C
JC
Westerman
L E
LE
Jensen
P E
PE
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
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