Talin1 regulates TCR-mediated LFA-1 function.
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.
Simonson
William T N
WT
Program in Cellular and Molecular Biology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Franco
Santos J
SJ
Huttenlocher
Anna
A
D000199:Actins / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D021381:Protein Transport / Q000276:immunology; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D016608:Talin / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D000199:Actins; D016169:Lymphocyte Function-Associated Antigen-1; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D016608:Talin