A conformation- and avidity-based proofreading mechanism for the TCR-CD3 complex.
During antigen recognition, T cells show high sensitivity and specificity, and a wide dynamic range. Paradoxically, these characteristics are based on low-affinity receptor-ligand interactions [between the T-cell antigen receptor (TCR-CD3) complex and the antigen peptide bound to MHC]. Recent evidence indicates that the TCR-CD3 is expressed as multivalent complexes in the membrane of non-stimulated T cells and that conformational changes in the TCR-CD3 can be induced by strong but not weak agonists. Here, we propose a thermodynamic model whereby the specificity of the TCR-CD3-pMHC interaction is explained by its multivalent nature. We also propose that the free energy barriers involved in the change in conformation of the receptor impose a response threshold and determine the kinetic properties of recognition. Finally, we suggest that multivalent TCR-CD3s can amplify signals by spreading them from pMHC-engaged TCR-CD3s to unengaged complexes as a consequence of the cooperativity in the system.
Schamel
Wolfgang W A
WW
Max Planck-Institut für Immunbiologie and University of Freiburg, Stübeweg 51, 79108 Freiburg, Germany.
Risueño
Ruth M
RM
Minguet
Susana
S
Ortíz
Angel R
AR
Alarcón
Balbino
B
D006801:Humans; D008024:Ligands; D018448:Models, Immunological; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D008024:Ligands; D017260:Receptor-CD3 Complex, Antigen, T-Cell