Brefeldin a implicates egress from endoplasmic reticulum in class i restricted antigen presentation


Brefeldin a implicates egress from endoplasmic reticulum in class i restricted antigen presentation

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ABSTRACT MOST antigens must be processed intracellularly before they can be presented, in association with major histocompatibility complex (MHC) molecules at the cell surface, for


recognition by the antigen-specific receptor of T cells1–3. This processing appears to involve cleavage of protein antigens to Smaller peptides4–7. Only certain fragments of any protein can


serve as T-cell epitopes and this is, at least in part, determined by the requirement that peptides be able to bind the MHC molecules8–10. Class I restricted antigens are derived from


proteins, such as viral antigens, that are synthesized within the presenting cell11–13.Many of these antigens are cytosolic proteins and recent evidence suggests that it is in the cytosol


that these proteins are processed to produce either the antigenic peptides or processed intermediates13–16. How and where these processed cytosolic antigens cross the membrane of the


vacuolar system and bind to the extracellular domain of the class I molecule is not known but one obvious site for this process is the endoplasmic reticulum (ER), because this organelle is


specialized to translocate proteins across the membrane from the cytosol into the secretory system. Based on this model, we reasoned that if we could pharmacologically block the movement of


proteins out of the ER, endogenous antigen presentation would cease. An agent which causes such an effect is available17,18 —the fungal antibiotic Brefeldin A (BFA). Consistent with the


above hypothesis, we report that BFA completely abolishes the ability of a cell to present endogenously synthesized antigens to class I restricted cytotoxic T cells. Access through your


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Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA AUTHORS AND AFFILIATIONS * Cell Biology and Metabolism Branch, National Institute of Child


Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20892, USA Jed G. Nuchtern, Juan S. Bonifacino, William E. Biddison & Richard D. Klausner Authors * Jed


G. Nuchtern View author publications You can also search for this author inPubMed Google Scholar * Juan S. Bonifacino View author publications You can also search for this author inPubMed 


Google Scholar * William E. Biddison View author publications You can also search for this author inPubMed Google Scholar * Richard D. Klausner View author publications You can also search


for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nuchtern, J., Bonifacino, J., Biddison, W. _et al._ Brefeldin A


implicates egress from endoplasmic reticulum in class I restricted antigen presentation. _Nature_ 339, 223–226 (1989). https://doi.org/10.1038/339223a0 Download citation * Received: 31


January 1989 * Accepted: 06 April 1989 * Issue Date: 18 May 1989 * DOI: https://doi.org/10.1038/339223a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this


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