Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action.

TitleCompartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action.
Publication TypeJournal Article
Year of Publication2010
AuthorsLev A, Princiotta MF, Zanker D, Takeda K, Gibbs JS, Kumagai C, Waffarn E, Dolan BP, Burgevin A, Van Endert P, Chen W, Bennink JR, Yewdell JW
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue15
Pagination6964-9
Date Published2010 Apr 13
ISSN1091-6490
KeywordsAnimals, Antigen Presentation, Binding, Competitive, CD8-Positive T-Lymphocytes, Cytosol, Flow Cytometry, Genes, MHC Class I, Histocompatibility Antigens Class I, Kinetics, Ligands, Mice, Models, Biological, Monitoring, Immunologic, Peptides, Protein Binding
Abstract

MHC class I molecules function to display peptides generated from cellular and pathogen gene products for immune surveillance by CD8(+) T cells. Cells typically express approximately 100,000 class I molecules, or approximately 1 per 30,000 cellular proteins. Given "one protein, one peptide" representation, immunosurveillance would be heavily biased toward the most abundant cell proteins. Cells use several mechanisms to prevent this, including the predominant use of defective ribosomal products (DRiPs) to generate peptides from nascent proteins and, as we show here, compartmentalization of DRiP peptide generation to prevent competition from abundant cytosolic peptides. This provides an explanation for the exquisite ability of T cells to recognize peptides generated from otherwise undetected gene products.

DOI10.1073/pnas.0910997107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.