Brefeldin A specifically inhibits presentation of protein antigens to cytotoxic T lymphocytes.
Cytotoxic T lymphocytes (CTLs) recognize foreign antigens, including viral proteins, in association with major histocompatibility complex (MHC) class I molecules. Brefeldin A, a specific inhibitor of exocytosis, completely and reversibly inhibited the presentation of viral proteins, but not exogenous peptides, to MHC class I-restricted CTLs directed against influenza virus antigens. The effect of brefeldin A on antigen presentation correlated with its inhibition of intracellular transport of newly synthesized class I molecules. Brefeldin A is thus a specific inhibitor of antigen processing for class I-restricted T cell recognition. Its effect on antigen presentation supports the idea that exogenous peptide antigens associate with cell surface class I molecules, whereas protein antigens processed via the cytosolic route associate with nascent class I molecules before they leave the trans-Golgi complex.
Yewdell
J W
JW
Laboratory for Viral Diseases, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852.
Bennink
J R
JR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A; D002462:Cell Membrane / Q000276:immunology; D003517:Cyclopentanes / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005089:Exocytosis / Q000187:drug effects; D006056:Golgi Apparatus / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D051379:Mice; D009698:Nucleoproteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014162:Transfection; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D003517:Cyclopentanes; D000939:Epitopes; D006183:H-2 Antigens; D006388:Hemagglutinins; D015395:Histocompatibility Antigens Class I; D009698:Nucleoproteins; D014764:Viral Proteins; D020126:Brefeldin A