Heat shock proteins implicated in antigen processing and presentation.
The recognition of antigen by helper T lymphocytes requires that the antigen be processed and presented by a cell expressing the Major Histocompatibility Complex (MHC) class II molecules. Antigen is taken into an acidic intracellular compartment where it is proteolytically degraded, releasing peptide fragments which become displayed on the cell surface in association with the MHC class II molecules. At present, little is known of the discrete steps in this process or the molecular mechanisms underlying the assembly of the antigenic peptide-MHC class II complex. Although antigenic peptides have been shown to bind directly to the MHC class II molecules, the unusual characteristics of this binding, namely extraordinarily slow association and dissociation rates, make it likely that the binding of peptide to MHC is facilitated within the cell by unknown mechanisms. The functions recently ascribed to several members of the heat shock proteins, in particular their binding to newly synthesized, denatured or inappropriately folded proteins, make them attractive candidates to play a role in antigen processing. In searching for proteins which might facilitate the binding of peptides to the MHC class II molecules, we isolated a peptide binding protein of 72/74 kDa Mr (PBP72/74). Antibodies raised to PBP72/74 block antigen processing and/or presentation, indicating a role for PBP72/74 in this process. Recent studies show that PBP72/74 is serologically related to the heat shock protein (hsp) family and that PBP72/74 shares a second characteristic of this family, namely ATP binding.(ABSTRACT TRUNCATED AT 250 WORDS)
De Nagel
D C
DC
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500.
Pierce
S K
SK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000939:Epitopes; D006360:Heat-Shock Proteins; D010455:Peptides