Inhibition by brefeldin A of presentation of exogenous protein antigens to MHC class II-restricted T cells.
Peptides bound to class I or class II major histocompatibility complex (MHC)-encoded molecules are ligands for the antigen-specific T-cell receptor of T-cells carrying the CD8 and CD4 antigens, respectively. MHC class I-restricted T cells generally recognize peptides derived from processing of endogenously synthesized cellular antigens, whereas class II-restricted T cells usually recognize peptides derived from exogenous antigens entering antigen presenting cells. Accordingly, two separate pathways of antigen processing and presentation have been proposed. The fungal metabolite brefeldin A (BFA), an inhibitor of protein transport from the endoplasmic reticulum, inhibits presentation of endogenous antigens for MHC-restricted T-cell recognition. The selectivity of BFA activity has been inferred to reflect presentation of a given antigen processed through the cytosolic or the endocytic route. Here we show that BFA also greatly inhibits the presentation of exogenous protein antigens by MHC class II molecules to T cells, indicating a broader effect of this drug on antigen presentation and an additional similarity between the two processing pathways. As cycloheximide, a protein synthesis inhibitor, also inhibits presentation of protein antigens to class II-restricted T cells, the data indicate that peptides generated by processing of exogenous proteins binds to newly synthesized class II molecules for presentation to T cells.
Adorini
L
L
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Ullrich
S J
SJ
Appella
E
E
Fuchs
S
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D020126:Brefeldin A; D002451:Cell Compartmentation / Q000187:drug effects; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D066298:In Vitro Techniques; D051379:Mice; D009113:Muramidase / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D003517:Cyclopentanes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D020126:Brefeldin A; D010047:Ovalbumin; D009113:Muramidase