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EMBO J. 2011 Sep 23;30(23):4712-27. doi: 10.1038/emboj.2011.333.

Regulation of integrin affinity on cell surfaces.

Author information

1
Department of Pathology, Harvard Medical School, Immune Disease Institute and Children's Hospital, Boston, MA, USA.

Abstract

Lymphocyte activation triggers adhesiveness of lymphocyte function-associated antigen-1 (LFA-1; integrin α(L)β(2)) for intercellular adhesion molecules (ICAMs) on endothelia or antigen-presenting cells. Whether the activation signal, after transmission through multiple domains to the ligand-binding αI domain, results in affinity changes for ligand has been hotly debated. Here, we present the first comprehensive measurements of LFA-1 affinities on T lymphocytes for ICAM-1 under a broad array of activating conditions. Only a modest increase in affinity for soluble ligand was detected after activation by chemokine or T-cell receptor ligation, conditions that primed LFA-1 and robustly induced lymphocyte adhesion to ICAM-1 substrates. By stabilizing well-defined LFA-1 conformations by Fab, we demonstrate the absolute requirement of the open LFA-1 headpiece for adhesiveness and high affinity. Interaction of primed LFA-1 with immobilized but not soluble ICAM-1 triggers energy-dependent affinity maturation of LFA-1 to an adhesive, high affinity state. Our results lend support to the traction or translational motion dependence of integrin activation.

PMID:
21946563
PMCID:
PMC3243613
DOI:
10.1038/emboj.2011.333
[Indexed for MEDLINE]
Free PMC Article

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