Contact-dependent T cell activation and T cell stopping require talin1

• Published in: The Journal of immunology (1950) Vol. 187; no. 12; pp. 6256 - 6267
• Main Authors: Wernimont, Sarah A, Wiemer, Andrew J, Bennin, David A, Monkley, Susan J, Ludwig, Thomas, Critchley, David R, Huttenlocher, Anna
• Format: Journal Article
• Language: English
• Published: United States 15-12-2011
• Subjects: Actins - metabolism; Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Communication - genetics; Cell Communication - immunology; Cell Polarity - genetics; Cell Polarity - immunology; Cell Proliferation; Cells, Cultured; Immunological Synapses - genetics; Immunological Synapses - immunology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocyte Function-Associated Antigen-1 - physiology; Mice; Mice, Knockout; Mice, Transgenic; Signal Transduction - genetics; Signal Transduction - immunology; Talin - deficiency; Talin - genetics; Talin - physiology; Vinculin - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1102028

T cell-APC contact initiates T cell activation and is maintained by the integrin LFA-1. Talin1, an LFA-1 regulator, localizes to the immune synapse (IS) with unknown roles in T cell activation. In this study, we show that talin1-deficient T cells have defects in contact-dependent T cell stopping and proliferation. Although talin1-deficient T cells did not form stable interactions with APCs, transient contacts were sufficient to induce signaling. In contrast to prior models, LFA-1 polarized to T cell-APC contacts in talin1-deficient T cells, but vinculin and F-actin polarization at the IS was impaired. These results indicate that T cell proliferation requires sustained, talin1-mediated T cell-APC interactions and that talin1 is necessary for F-actin polarization and the stability of the IS.