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Proc Natl Acad Sci U S A. 2012 May 1;109(18):7025-30. doi: 10.1073/pnas.1112387109. Epub 2012 Apr 16.

MHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA.

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Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


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.

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