Cerulenin is a potent inhibitor of antigen processing by antigen-presenting cells.
Cerulenin is an antibiotic that inhibits eukaryotic lipid and sterol synthesis and blocks lipid modification of proteins. The effect of cerulenin on the ability of accessory cells to present antigen to T cells was investigated. This antibiotic strongly inhibits the ability of accessory cells to present antigen to murine T-T hybrids. This effect is observed for multiple distinct antigens including L-glutamic acid60-L-alanine30-L-tyrosine10, bovine insulin, L-glutamic acid56-L-lysine35-L-phenylalanine9, and ovalbumen. Presentation by both macrophage and B lymphoblastoid cell lines is inhibited. The ability to effectively pulse these cells with antigen is inhibited but not the ability of these same cells to present antigen that they have previously processed. Furthermore, this inhibition is selective as it can occur without significant inhibition of the antigen-presenting cell protein or DNA synthesis. Cerulenin does not inhibit antigen uptake or catabolism as assessed with labeled antigen. By these criteria this drug is shown to interfere with an antigen-processing step. The ability of cerulenin to block processing was compared with other known inhibitors. Although cerulenin was effective with all antigens tested, at least one inhibitor was not. Taken together, these results suggest that the effect of cerulenin may define a distinct step in antigen processing and provides evidence that some other processing events are not universally required. The ability of cerulenin to interfere with antigen processing is discussed in the context of the known actions of this antibiotic and events of antigen processing and presentation.
Falo
L D
LD
Department of Pathology, Harvard Medical School, Boston, MA 02115.
Benacerraf
B
B
Rothstein
L
L
Rock
K L
KL
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D002460:Cell Line; D002569:Cerulenin / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D003864:Depression, Chemical; D008213:Lymphocyte Activation; D051379:Mice; D008985:Monensin / Q000494:pharmacology
D000935:Antifungal Agents; D000941:Antigens; D000643:Ammonium Chloride; D002569:Cerulenin; D002738:Chloroquine; D008985:Monensin