The mechanism of action of tapasin in the peptide exchange on MHC class I molecules determined from kinetics simulation studies.
To understand the mechanism of action of the chaperone protein tapasin, which mediates loading of high-affinity peptides onto major histocompatibility complex (MHC) class I molecules in the antiviral immune response, we have performed numerical simulations of the class I-peptide binding process with four different mechanistic hypotheses from the literature, and tested our predictions by laboratory experiments. We find - in agreement of experimental and theoretical studies - that class I-peptide binding in cells is generally under kinetic control, and that tapasin introduces partial thermodynamic control to the process by competing with peptide for binding to class I. Based on our results, we suggest further experimental directions.
Biochemistry and Cell Biology, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
Clemens
C
Schneeweiss
Malgorzata
M
Garstka
James
J
Smith
Marc-Thorsten
MT
Hütt
Sebastian
S
Springer
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D003198:Computer Simulation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000276:immunology*; D051379:Mice; D008954:Models, Biological; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding
D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin