Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest.
Proc Natl Acad Sci U S A
; 112(39): 12151-6, 2015 Sep 29.
Article
em En
| MEDLINE
| ID: mdl-26371316
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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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Antígenos de Diferenciação de Linfócitos T
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Movimento Celular
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Microambiente Celular
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Imunidade Celular
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article