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 |
Volume | 109 |
Issue | 18 |
Pagination | 7025-30 |
Date Published | 2012 May 1 |
Keywords | RNA, Viral |
Abstract | 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. |
DOI | 10.1073/pnas.1112387109 |