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Journal articles
Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest
Abstract : T lymphocytes are highly motile cells that decelerate upon antigen recognition. These cells can either completely stop or maintain a low level of motility, forming contacts referred to as synapses or kinapses, respectively. Whether similar or distinct molecular mechanisms regulate T-cell deceleration during synapses or kinapses is unclear. Here, we used microfabricated channels and intravital imaging to observe and manipulate T-cell kinapses and synapses. We report that high-affinity antigen induced a pronounced deceleration selectively dependent on Ca 2+ signals and actin-related protein 2/3 complex (Arp2/3) activity. In contrast, low-affinity antigens induced a switch of migration mode that promotes T-cell exploratory behavior, characterized by partial deceleration and frequent direction changes. This switch depended on T-cell receptor binding but was largely independent of downstream signaling. We propose that distinct mechanisms of T-cell deceleration can be triggered during antigenic recognition to favor local exploration and signal integration upon suboptimal stimulus and complete arrest on the best antigen-presenting cells.
Cited literature [27 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01238129
Contributor : Philippe Bousso Connect in order to contact the contributor
Submitted on : Friday, December 4, 2015 - 1:02:32 PM
Last modification on : Wednesday, October 27, 2021 - 3:00:19 PM
Long-term archiving on: : Saturday, April 29, 2017 - 6:11:40 AM
Contributor : Philippe Bousso Connect in order to contact the contributor
Submitted on : Friday, December 4, 2015 - 1:02:32 PM
Last modification on : Wednesday, October 27, 2021 - 3:00:19 PM
Long-term archiving on: : Saturday, April 29, 2017 - 6:11:40 AM
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PNAS-2015-Moreau-12151-6.pdf
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