Intracellular rate-limiting steps in MHC class I antigen processing.
Quantitative aspects of the endogenous pathway of Ag processing and presentation by MHC class I molecules to CD8+ CTL were analyzed over a wide range of Ag expression in recombinant vaccinia virus-infected cells expressing beta-galactosidase as model Ag. Only the amount of starting Ag was varied, leaving other factors unaltered. Below a certain level of Ag synthesis, increasing protein amounts led to a sharp rise in recognition by CTL. Higher levels of Ag expression led to a saturation point, which intracellularly limited the number of naturally processed peptides bound to MHC and thereby also CTL recognition. The rate-limiting step was located at the binding of the antigenic peptide to MHC inside the vaccinia virus-infected cell or before this event.
Montoya
M
M
Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Madrid, Spain.
Del Val
M
M
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism*; D007700:Kinetics; D012515:Mast-Cell Sarcoma / Q000201:enzymology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D001616:beta-Galactosidase