Open AccessCompartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action
Author(s) -
Avital Lev,
Michael F. Princiotta,
Damien Zanker,
Kazuyo Takeda,
James S. Gibbs,
Chiharu Kumagai,
Elizabeth Waffarn,
Brian P. Dolan,
Anne Burgevin,
Peter Van Endert,
Weisan Chen,
Jack R. Bennink,
Jonathan W. Yewdell
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0910997107
Subject(s) - mhc class i , immunosurveillance , cd8 , biology , major histocompatibility complex , microbiology and biotechnology , transporter associated with antigen processing , antigen processing , peptide , immune system , biochemistry , genetics
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 ∼100,000 class I molecules, or ∼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.