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

TitleMHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA.
Publication TypeJournal Article
Year of Publication2012
AuthorsDolan BP, Sharma AA, Gibbs JS, Cunningham TJ, Bennink JR, Yewdell JW
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue18
Pagination7025-30
Date Published2012 May 1
ISSN1091-6490
KeywordsAnimals, Antigen Presentation, Base Sequence, Cell Line, Hela Cells, Histocompatibility Antigens Class I, Humans, Mice, Ovalbumin, Peptide Fragments, Protein Biosynthesis, RNA, Messenger, 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.

DOI10.1073/pnas.1112387109
Alternate JournalProc. Natl. Acad. Sci. U.S.A.