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The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells.

G A Van Seventer, Y Shimizu, K J Horgan and S Shaw
J Immunol June 15, 1990, 144 (12) 4579-4586;
G A Van Seventer
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Y Shimizu
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K J Horgan
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S Shaw
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Abstract

Functional studies demonstrate that T cell activation often requires not only occupancy of the TCR but costimulatory interactions of other molecules, which remain largely undefined. We have tested the hypothesis that LFA-1 interaction with its ligand intercellular adhesion molecule 1 (CD54) (ICAM-1) is such a costimulatory interaction in a model system using biochemically purified ICAM-1 and TCR cross-linking by anti-CD3 mAb OKT3 immobilized on plastic. Resting T cells do not respond to OKT3 mAb immobilized on plastic. However ICAM-1 deposited on plastic together with the nonmitogenic immobilized OKT3 results in a potent activating stimulus. This costimulation cannot be readily accounted for by ICAM-1-mediated adhesion but is consistent with a role in signaling, which is observed in ICAM-1-mediated augmentation of activation induced by PMA/ionomycin. The ability of ICAM-1 to costimulate with immobilized CD3 contrasts with minimal costimulatory activity of cytokines IL-1 beta, IL-2, and IL-6. The proliferative response to co-immobilized OKT3 and ICAM-1 is dependent on the IL-2R, which is induced only in the presence of both OKT3 and ICAM-1. The present data demonstrate that LFA-1/ICAM-1 interaction is a potent costimulus for TCR-mediated activation; this observation, interpreted in light of previous reports, suggests that LFA-1/ICAM-1 is of major physiologic importance as a costimulatory signal.

  • Copyright © 1990 by American Association of Immunologists
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The Journal of Immunology
Vol. 144, Issue 12
15 Jun 1990
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The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells.
G A Van Seventer, Y Shimizu, K J Horgan, S Shaw
The Journal of Immunology June 15, 1990, 144 (12) 4579-4586;

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The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells.
G A Van Seventer, Y Shimizu, K J Horgan, S Shaw
The Journal of Immunology June 15, 1990, 144 (12) 4579-4586;
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Print ISSN 0022-1767        Online ISSN 1550-6606