Talin1 regulates TCR-mediated LFA-1 function.
J Immunol
; 177(11): 7707-14, 2006 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-17114441
ABSTRACT
The leukocyte integrin LFA-1 plays a critical role in T cell trafficking and T cell adhesion to APCs. It is known that integrin-mediated adhesion is regulated by changes in integrin ligand-binding affinity and valency through inside-out signaling. However, the molecular mechanisms involved in TCR-mediated LFA-1 regulation are not well understood. In this study, we show that the cytoskeletal protein talin1 is required for TCR-mediated activation of LFA-1 through regulation of LFA-1 affinity and clustering. Depletion of talin1 from human T cells by small interfering RNAs impairs TCR-induced adhesion to ICAM-1 and T cell-APC conjugation. TCR-induced LFA-1 polarization, but not actin polarization, is defective in talin1-deficient T cells. Although LFA-1 affinity is also reduced in talin1-deficient T cells, rescue of LFA-1 affinity alone is not sufficient to restore LFA-1 adhesive function. Together, our findings indicate that TCR-induced up-regulation of LFA-1-dependent adhesiveness and resulting T cell-APC conjugation require talin1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
/
Linfócitos T
/
Comunicação Celular
/
Antígeno-1 Associado à Função Linfocitária
/
Talina
/
Células Apresentadoras de Antígenos
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos