Single molecule methods to measure receptor–ligand interaction in immunological synapses

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Item Type:	Book Section
Title:	Single molecule methods to measure receptor–ligand interaction in immunological synapses
Creators Name:	Huppa, J.B. and Schütz, G.J.
Abstract:	T-cell antigen recognition requires the formation of an immunological synapse, a transient interface between a T-lymphocyte and an antigen presenting cell (APC). It is within this complex and dynamic bi-membranous contact where T-cell antigen receptors (TCRs) on the T-cell bind their cognate ligands, i.e., antigenic peptides embedded within major histocompatibility complex molecules (pMHC), on the APC. Productive TCR engagement is key to initiating signaling pathways required for the activation of T-cell effector mechanisms, and hence a lot of attention has been focused on the structural and biophysical properties of the binding partners involved. However, one central question remains unanswered: how can one explain the exquisite sensitivity and selectivity of T-cells toward antigen, which is ultimately based on short-lived TCR–pMHC interactions with moderate affinities? To approach this problem in a comprehensive manner it seems logical to study TCR–pMHC binding in situ, that is, within the immunological synapse, where receptors and ligands unfold their function. The last decade has seen a surge in the use of live-cell approaches involving advanced molecular imaging and other biophysical methodologies with single molecule resolution. Here we will review how such modalities have lent a new perspective on molecular interactions in situ and how they have changed the way we look at T-cell antigen recognition.
Series Name:	Reference Module in Biomedical Sciences
Title of Book:	Encyclopedia of Cell Biology
ISBN:	978-0-12-394796-3
Publisher:	Elsevier
Volume:	3
Page Range:	660-666
Number of Pages:	7
Date:	2016
Official Publication:	https://doi.org/10.1016/B978-0-12-394447-4.30098-0

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