Force generation upon T cell receptor engagement.

T cells are major players of adaptive immune response in mammals. Recognition of an antigenic peptide in association with the major histocompatibility complex at the surface of an antigen presenting cell (APC) is a specific and sensitive process whose mechanism is not fully understood. The potential...

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Autores principales:	Julien Husson, Karine Chemin, Armelle Bohineust, Claire Hivroz, Nelly Henry
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de40cee34ee64cf6af8b9ea27963b453
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id	oai:doaj.org-article:de40cee34ee64cf6af8b9ea27963b453
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spelling	oai:doaj.org-article:de40cee34ee64cf6af8b9ea27963b4532021-11-18T06:54:13ZForce generation upon T cell receptor engagement.1932-620310.1371/journal.pone.0019680https://doaj.org/article/de40cee34ee64cf6af8b9ea27963b4532011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21572959/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203T cells are major players of adaptive immune response in mammals. Recognition of an antigenic peptide in association with the major histocompatibility complex at the surface of an antigen presenting cell (APC) is a specific and sensitive process whose mechanism is not fully understood. The potential contribution of mechanical forces in the T cell activation process is increasingly debated, although these forces are scarcely defined and hold only limited experimental evidence. In this work, we have implemented a biomembrane force probe (BFP) setup and a model APC to explore the nature and the characteristics of the mechanical forces potentially generated upon engagement of the T cell receptor (TCR) and/or lymphocyte function-associated antigen-1 (LFA-1). We show that upon contact with a model APC coated with antibodies towards TCR-CD3, after a short latency, the T cell developed a timed sequence of pushing and pulling forces against its target. These processes were defined by their initial constant growth velocity and loading rate (force increase per unit of time). LFA-1 engagement together with TCR-CD3 reduced the growing speed during the pushing phase without triggering the same mechanical behavior when engaged alone. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was monitored simultaneously to verify the cell commitment in the activation process. [Ca(2+)](i) increased a few tens of seconds after the beginning of the pushing phase although no strong correlation appeared between the two events. The pushing phase was driven by actin polymerization. Tuning the BFP mechanical properties, we could show that the loading rate during the pulling phase increased with the target stiffness. This indicated that a mechanosensing mechanism is implemented in the early steps of the activation process. We provide here the first quantified description of force generation sequence upon local bidimensional engagement of TCR-CD3 and discuss its potential role in a T cell mechanically-regulated activation process.Julien HussonKarine CheminArmelle BohineustClaire HivrozNelly HenryPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19680 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julien Husson Karine Chemin Armelle Bohineust Claire Hivroz Nelly Henry Force generation upon T cell receptor engagement.
description	T cells are major players of adaptive immune response in mammals. Recognition of an antigenic peptide in association with the major histocompatibility complex at the surface of an antigen presenting cell (APC) is a specific and sensitive process whose mechanism is not fully understood. The potential contribution of mechanical forces in the T cell activation process is increasingly debated, although these forces are scarcely defined and hold only limited experimental evidence. In this work, we have implemented a biomembrane force probe (BFP) setup and a model APC to explore the nature and the characteristics of the mechanical forces potentially generated upon engagement of the T cell receptor (TCR) and/or lymphocyte function-associated antigen-1 (LFA-1). We show that upon contact with a model APC coated with antibodies towards TCR-CD3, after a short latency, the T cell developed a timed sequence of pushing and pulling forces against its target. These processes were defined by their initial constant growth velocity and loading rate (force increase per unit of time). LFA-1 engagement together with TCR-CD3 reduced the growing speed during the pushing phase without triggering the same mechanical behavior when engaged alone. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was monitored simultaneously to verify the cell commitment in the activation process. [Ca(2+)](i) increased a few tens of seconds after the beginning of the pushing phase although no strong correlation appeared between the two events. The pushing phase was driven by actin polymerization. Tuning the BFP mechanical properties, we could show that the loading rate during the pulling phase increased with the target stiffness. This indicated that a mechanosensing mechanism is implemented in the early steps of the activation process. We provide here the first quantified description of force generation sequence upon local bidimensional engagement of TCR-CD3 and discuss its potential role in a T cell mechanically-regulated activation process.
format	article
author	Julien Husson Karine Chemin Armelle Bohineust Claire Hivroz Nelly Henry
author_facet	Julien Husson Karine Chemin Armelle Bohineust Claire Hivroz Nelly Henry
author_sort	Julien Husson
title	Force generation upon T cell receptor engagement.
title_short	Force generation upon T cell receptor engagement.
title_full	Force generation upon T cell receptor engagement.
title_fullStr	Force generation upon T cell receptor engagement.
title_full_unstemmed	Force generation upon T cell receptor engagement.
title_sort	force generation upon t cell receptor engagement.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/de40cee34ee64cf6af8b9ea27963b453
work_keys_str_mv	AT julienhusson forcegenerationupontcellreceptorengagement AT karinechemin forcegenerationupontcellreceptorengagement AT armellebohineust forcegenerationupontcellreceptorengagement AT clairehivroz forcegenerationupontcellreceptorengagement AT nellyhenry forcegenerationupontcellreceptorengagement
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Force generation upon T cell receptor engagement.

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