A group-specific inhibitor of lysosomal cysteine proteinases selectively inhibits both proteolytic degradation and presentation of the antigen dinitrophenyl-poly-L-lysine by guinea pig accessory cells to T cells.
A limited intralysosomal proteolytic degradation is probably a key event in the accessory cell processing of large protein antigens before their presentation to T cells. With the aid of highly specific inhibitors of proteinases, we have examined the role of proteolysis in the presentation of antigens by guinea pig accessory cells. The proteinase inhibitor benzyloxycarbonyl-phenylalanylalanine-diazomethyl-ketone, which selectively inhibits cysteine proteinases, was used to block this set of enzymes in cultured cells. We demonstrate that the selective inhibition of the cysteine proteinases of antigen-presenting cells causes a profound inhibition of both the proteolytic degradation and the presentation of the synthetic antigen dinitrophenyl-poly-L-lysine. In contrast, the presentation of another synthetic antigen, the copolymer of L-glutamic acid and L-alanine, was enhanced by the same inhibitor. Another inhibitor, pepstatin A, which selectively blocks aspartic proteinases, did not block the presentation of dinitrophenyl-poly-L-lysine. The results identify cysteine proteinases, probably lysosomal, as one of the groups of enzymes involved in antigen processing.
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology* / Q000276:immunology; D001667:Binding, Competitive; D015853:Cysteine Proteinase Inhibitors; D004140:Dinitrophenols / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D010436:Pepstatins / Q000494:pharmacology; D010455:Peptides / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology; D011107:Polylysine / Q000276:immunology* / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology
D015853:Cysteine Proteinase Inhibitors; D004140:Dinitrophenols; D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins; D010436:Pepstatins; D010455:Peptides; D011506:Proteins; D014373:Tuberculin; C014195:Streptomyces pepsin inhibitor; D011107:Polylysine; C027606:L-glutamic acid-L-tyrosine copolymer; C034117:N-benzyloxycarbonyllysine 4-nitrophenyl ester; D008239:Lysine; C031375:pepstatin