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Título

Receptor Pre-Clustering and T cell Responses: Insights into Molecular Mechanisms

AutorCastro, Mario; Santen, Hisse M. van; Férez, María; Alarcón, Balbino; Lythe, Grant; Molina-Paris, C.
Fecha de publicación30-abr-2014
EditorFrontiers Media
CitaciónFront. Immunol. 5: 132 (2014)
ResumenT cell activation, initiated by T cell receptor (TCR) mediated recognition of pathogen-derived peptides presented by major histocompatibility complex class I or II molecules (pMHC), shows exquisite specificity and sensitivity, even though the TCR–pMHC binding interaction is of low affinity. Recent experimental work suggests that TCR pre-clustering may be a mechanism via which T cells can achieve such high sensitivity. The unresolved stoichiometry of the TCR makes TCR–pMHC binding and TCR triggering, an open question. We formulate a mathematical model to characterize the pre-clustering of T cell receptors (TCRs) on the surface of T cells, motivated by the experimentally observed distribution of TCR clusters on the surface of naive and memory T cells. We extend a recently introduced stochastic criterion to compute the timescales of T cell responses, assuming that ligand-induced cross-linked TCR is the minimum signaling unit. We derive an approximate formula for the mean time to signal initiation. Our results show that pre-clustering reduces the mean activation time. However, additional mechanisms favoring the existence of clusters are required to explain the difference between naive and memory T cell responses. We discuss the biological implications of our results, and both the compatibility and complementarity of our approach with other existing mathematical models.
Versión del editorhttp://dx.doi.org/10.3389/fimmu.2014.00132
URIhttp://hdl.handle.net/10261/153158
DOI10.3389/fimmu.2014.00132
ISSN1664-3224
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