title: A conformation- and avidity-based proofreading mechanism for the TCR-CD3 complex.
abstract: 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.
authors.affiliation: Max Planck-Institut für Immunbiologie and University of Freiburg, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Wolfgang W A
authors.initials: WW
authors.lastname: Schamel
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Risueño
authors.forename: Susana
authors.initials: S
authors.lastname: Minguet
authors.forename: Angel R
authors.initials: AR
authors.lastname: Ortíz
authors.forename: Balbino
authors.initials: B
authors.lastname: Alarcón
mesh_terms: D006801:Humans; D008024:Ligands; D018448:Models, Immunological; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D017260:Receptor-CD3 Complex, Antigen, T-Cell