Cutting edge: Evidence for a dynamically driven T cell signaling mechanism
Authors
Hawse, William F.Champion, Matthew M.
Joyce, Michelle V.
Hellman, Lance M.
Hossain, Moushumi
Ryan, Veronica
Pierce, Brian G.
Weng, Zhiping
Baker, Brian M.
UMass Chan Affiliations
Program in Bioinformatics and Integrative BiologyDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2012-06-15Keywords
AnimalsComputational Biology
HLA-A2 Antigen
Humans
Lymphocyte Activation
Peptide Fragments
Protein Structure, Quaternary
Receptors, Antigen, T-Cell
Signal Transduction
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Surface Plasmon Resonance
T-Lymphocytes
Urokinase-Type Plasminogen Activator
Bioinformatics
Computational Biology
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
T cells use the alphabeta TCR to bind peptides presented by MHC proteins (pMHC) on APCs. Formation of a TCR-pMHC complex initiates T cell signaling via a poorly understood process, potentially involving changes in oligomeric state, altered interactions with CD3 subunits, and mechanical stress. These mechanisms could be facilitated by binding-induced changes in the TCR, but the nature and extent of any such alterations are unclear. Using hydrogen/deuterium exchange, we demonstrate that ligation globally rigidifies the TCR, which via entropic and packing effects will promote associations with neighboring proteins and enhance the stability of existing complexes. TCR regions implicated in lateral associations and signaling are particularly affected. Computational modeling demonstrated a high degree of dynamic coupling between the TCR constant and variable domains that is dampened upon ligation. These results raise the possibility that TCR triggering could involve a dynamically driven, allosteric mechanism.Source
J Immunol. 2012 Jun 15;188(12):5819-23. doi: 10.4049/jimmunol.1200952. Link to article on publisher's siteDOI
10.4049/jimmunol.1200952Permanent Link to this Item
http://hdl.handle.net/20.500.14038/25838PubMed ID
22611242Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.1200952