Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest - Institut Pasteur Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2015

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.
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Dates and versions

pasteur-01238129 , version 1 (04-12-2015)

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Hélène D. Moreau, Fabrice Lemaître, Kym R Garrod, Zacarias Garcia, Ana-Maria Lennon-Duménil, et al.. Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112 (39), pp.12151-6. ⟨10.1073/pnas.1506654112⟩. ⟨pasteur-01238129⟩
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