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MHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA.
|Title||MHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Dolan BP, Sharma AA, Gibbs JS, Cunningham TJ, Bennink JR, Yewdell JW|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Date Published||2012 May 1|
|Keywords||Animals, Antigen Presentation, Base Sequence, Cell Line, Hela Cells, Histocompatibility Antigens Class I, Humans, Mice, Ovalbumin, Peptide Fragments, Protein Biosynthesis, RNA, Messenger, RNA, Viral|
To better understand the generation of MHC class I-associated peptides, we used a model antigenic protein whose proteasome-mediated degradation is rapidly and reversibly controlled by Shield-1, a cell-permeant drug. When expressed from a stably transfected gene, the efficiency of antigen presentation is ~2%, that is, one cell-surface MHC class I-peptide complex is generated for every 50 folded source proteins degraded upon Shield-1 withdrawal. By contrast, when the same protein is expressed by vaccinia virus, its antigen presentation efficiency is reduced ~10-fold to values similar to those reported for other vaccinia virus-encoded model antigens. Virus infection per se does not modify the efficiency of antigen processing. Rather, the efficiency difference between cellular and virus-encoded antigens is based on whether the antigen is synthesized from transgene- vs. virus-encoded mRNA. Thus, class I antigen-processing machinery can distinguish folded proteins based on the precise details of their synthesis to modulate antigen presentation efficiency.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|