F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse.

ABSTRACT: Integrin-dependent interactions between T cells and antigen-presenting cells are vital for proper T cell activation, effector function, and memory. Regulation of integrin function occurs via conformational change, which modulates ligand affinity, and receptor clustering, which modulates valency. Here, we show that conformational intermediates of leukocyte functional antigen 1 (LFA-1) form a concentric array at the immunological synapse. Using an inhibitor cocktail to arrest F-actin dynamics, we show that organization of this array depends on F-actin flow and ligand mobility. Furthermore, F-actin flow is critical for maintaining the high affinity conformation of LFA-1, for increasing valency by recruiting LFA-1 to the immunological synapse, and ultimately for promoting intracellular cell ad

SUBMITTER: Comrie WA 

PROVIDER: S-EPMC4332248 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature