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Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest. | LitMetric

Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest.

Proc Natl Acad Sci U S A

Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France; INSERM U668, 75015 Paris, France;

Published: September 2015

AI Article Synopsis

  • T lymphocytes slow down their movement when they recognize antigens, forming special contacts known as synapses or kinapses, which are characterized by different levels of motility.
  • Researchers used advanced imaging techniques to study these interactions and found that high-affinity antigens caused T-cells to significantly decelerate, relying on calcium signals and the Arp2/3 protein complex.
  • Conversely, low-affinity antigens led to a change in T-cell movement, promoting exploratory behavior with less deceleration, indicating that T-cells have varied strategies for responding to different antigen strengths.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593123PMC
http://dx.doi.org/10.1073/pnas.1506654112DOI Listing

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