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Analysis of serial engagement and peptide-MHC transport in T cell receptor microclusters
by
Omer Dushek
University of British Columbia
Coauthors: Daniel Coombs
During stimulation of a T cell by an antigen-presenting-cell (APC) bearing cognate peptide-major-histocompatibility complexes (pMHC), T cell receptors (TCR) have been shown to form stable micrometer-scale clusters in the contact region. pMHC molecules diffusing in the APC membrane may bind and unbind from multiple TCR in a cluster. Such serial engagements of multiple TCR by a single pMHC have been hypothesized to be important in T cell signal amplification. We use mathematical modeling to characterize the number of clustered TCR bound by a single pMHC. We show that the TCR-pMHC bond kinetics alone do not allow substantial serial engagement of TCR and suggest molecules that could enhance TCR engagements. Mathematical tools: MFP calculations, asymptotic analysis, numerical solutions of PDEs.
Date received: April 11, 2008
Copyright © 2008 by the author(s). The author(s) of this document and the organizers of the conference have granted their consent to include this abstract in Atlas Conferences Inc. Document # cawd-23.