UNSPECIFIED. (2002) Quantifying the strength of ligand antagonism in TCR triggering. BULLETIN OF MATHEMATICAL BIOLOGY, 64 (4). pp. 781-808. ISSN 0092-8240

Full text not available from this repository.

Abstract

Triggering of the T cell receptor (TCR) may be antagonized by ligands that are slight variants of the immunogenic peptide. This paper proposes a mathematical model to quantify the strength of the antagonistic effect. The model is based on the kinetics of association and dissociation of TCR and peptide/major histocompatibility (pMHC) molecules, and incorporates TCR triggering according to a kinetic proofreading mechanism. Model analysis indicates that while the average lifetime of the TCR/pMHC complex is the basic determinant of the contribution to TCR triggering made by the ligand, the affinity of the ligand and its MHC presentation level are also important. However, these contributions depend on the kinetic limitation regime. There is a continuum of limitation regimes, at the extremes of which are found TCR limitation and MHC limitation. Both ligand affinity and TCR and pMHC densities determine whether TCR triggering is TCR limited or MHC limited. The changing importance of affinity and antigen presentation level under various kinetic limitation regimes may explain the respective roles of antagonistic and agonistic self peptides in thymic selection. Moreover, TCR down-regulation under TCR-limited conditions may allow the T cell to differentiate between the average lifetime of the TCR/pMHC complex and the presentation level of the ligand. A method for experimental differentiation between passive and active antagonistic effects is proposed which exploits the differences between TCR and MHC limitation. (C) 2002 Society for Mathematical Biology. Published by Elsevier Science Ltd. All rights reserved.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology
Journal or Publication Title:	BULLETIN OF MATHEMATICAL BIOLOGY
Publisher:	ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
ISSN:	0092-8240
Date:	July 2002
Volume:	64
Number:	4
Number of Pages:	28
Page Range:	pp. 781-808
Identification Number:	10.1006/bulm.2002.0302
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/10626

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item