title: MHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA.
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.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Dolan
authors.forename: Aditi A
authors.initials: AA
authors.lastname: Sharma
authors.forename: James S
authors.initials: JS
authors.lastname: Gibbs
authors.forename: Tshaka J
authors.initials: TJ
authors.lastname: Cunningham
authors.forename: Jack R
authors.initials: JR
authors.lastname: Bennink
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; C110366:OVA-8; D010446:Peptide Fragments; D012333:RNA, Messenger; D012367:RNA, Viral; D010047:Ovalbumin