title: Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action.
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.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Avital
authors.initials: A
authors.lastname: Lev
authors.forename: Michael F
authors.initials: MF
authors.lastname: Princiotta
authors.forename: Damian
authors.initials: D
authors.lastname: Zanker
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Takeda
authors.forename: James S
authors.initials: JS
authors.lastname: Gibbs
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kumagai
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Waffarn
authors.forename: Brian P
authors.initials: BP
authors.lastname: Dolan
authors.forename: Anne
authors.initials: A
authors.lastname: Burgevin
authors.forename: Peter
authors.initials: P
authors.lastname: Van Endert
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
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; D001667:Binding, Competitive; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D015166:Monitoring, Immunologic / Q000379:methods; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides