Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action.
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.
Lev
Avital
A
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Princiotta
Michael F
MF
Zanker
Damian
D
Takeda
Kazuyo
K
Gibbs
James S
JS
Kumagai
Chiharu
C
Waffarn
Elizabeth
E
Dolan
Brian P
BP
Burgevin
Anne
A
Van Endert
Peter
P
Chen
Weisan
W
Bennink
Jack R
JR
Yewdell
Jonathan W
JW
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
D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides