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First published online November 3, 2003
doi: 10.1242/10.1242/jcs.00876

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T-cell integrins: more than just sticking points

Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK

View larger version (32K): [in a new window]   Fig. 1. The multistep model of T-cell migration. T cells migrate from the blood, across the vascular endothelium into infected tissue or into lymph node (LN). The receptors involved in stages 1-6 are indicated in tabular form. The process of crossing the endothelial barrier into infected tissue or LN is similar. However, in LN, T cells crawl within a network of fibroblastic reticular cell-coated cables and, in infected tissues, they migrate along matrices composed chiefly of collagen fibrils. Abbreviations: CCL, chemokine ligand; CCR, chemokine receptor; PBM, perivascular basement membrane;?, lack of information.

View larger version (30K): [in a new window]   Fig. 2. Integrin activation. An integrin achieves higher affinity for ligand through conformational change or gains strength of binding through clustering (avidity). These two states can be accomplished experimentally through binding of Mg2+, Mn2+, activating mAbs or treatment with phorbol ester or crosslinking TCR. Gene modification of ADAP, SKAP-55 or Vav-1 (complexed with SLP-76; blue) demonstrates their role in integrin clustering. Calpain, GTPases Rac and Rap1, and the Rap1-binding protein RAPL also participate in integrin clustering. Signalling through chemokine receptors to pertussis-toxin-sensitive G proteins can cause a transient increase in integrin affinity. See text for references.

View larger version (26K): [in a new window]   Fig. 3. LFA-1-mediated migration of T cells on ICAM-1. Time-lapse video microscopy (x40 magnification) of a primary human T cell in contact with immobilized ICAM-1. The time in seconds after the first contact with ICAM-1 is depicted in each frame: initial contact (time=0), T-cell polarization (time=60-160 seconds) and migration (time=200 seconds) (Smith et al., 2003). Data reproduced with kind permission of Andrew Smith, Cancer Research, UK.

View larger version (112K): [in a new window]   Fig. 4. Kinases involved in LFA-1-mediated migration. Signalling through LFA-1 results in major changes in the T-cell morphology leading to migration. There are two compartments of myosin motor activity. At the leading edge, T-cell attachment and lamellipodial extension is dependent upon myosin, which is activated by MLCK. At the rear of the cell, myosin activated by RhoA and ROCK results in detachment of the trailing edge. The association of PKCßI with microtubules promotes T-cell migration (see text for details and references).

View larger version (32K): [in a new window]   Fig. 5. Signalling through integrins: the paxillin/CasL/CrkL pathway. The CasL/CrkL adaptor complex is formed by signalling through 4ß1, 4ß7 and LFA-1 on T cells. The figure generalizes the interactions following integrin activation, not all of which have been demonstrated for each T-cell integrin (see text for details).