A window of opportunity for cooperativity in the T Cell Receptor

Abstract

The T-cell antigen receptor (TCR) is pre-organised in oligomers, known as nanoclusters. Nanoclusters could provide a framework for inter-TCR cooperativity upon peptide antigen-major histocompatibility complex (pMHC) binding. Here we have used soluble pMHC oligomers in search for cooperativity effects along the plasma membrane plane. We find that initial binding events favour subsequent pMHC binding to additional TCRs, during a narrow temporal window. This behaviour can be explained by a 3-state model of TCR transition from Resting to Active, to a final Inhibited state. By disrupting nanoclusters and hampering the Active conformation, we show that TCR cooperativity is consistent with TCR nanoclusters adopting the Active state in a coordinated manner. Preferential binding of pMHC to the Active TCR at the immunological synapse suggests that there is a transient time frame for signal amplification in the TCR, allowing the T cells to keep track of antigen quantity and binding time.

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Item Type:	Article
Authors/Creators:	Martin-Blanco, N Blanco, R Alda-Catalinas, C Rodriguez-Bovolenta, E Oeste, CL Palmer, E Schamel, WW Lythe, G https://orcid.org/0000-0001-7966-5571 Molina-Paris, C https://orcid.org/0000-0001-9828-6737 Castro, M Alarcon, B
Copyright, Publisher and Additional Information:	© The Author(s) 2018 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
Dates:	Accepted: 10 June 2018 Published (online): 5 July 2018 Published: 5 July 2018
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Mathematics (Leeds) > Applied Mathematics (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	31 May 2018 09:10
Last Modified:	09 Sep 2020 17:27
Status:	Published
Publisher:	Springer Nature
Identification Number:	10.1038/s41467-018-05050-6
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:131507

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A window of opportunity for cooperativity in the T Cell Receptor

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