The Journal of Immunology, Vol 159, Issue 6 2685-2692, Copyright © 1997 by American Association of Immunologists

ARTICLES

Low affinity of cell surface lymphocyte function-associated antigen-1 (LFA-1) generates selectivity for cell-cell interactions

G Ganpule, R Knorr, JM Miller, CP Carron and ML Dustin
Center for Immunology and the Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.

We examined binding of soluble intercellular adhesion molecule-1 (ICAM- 1) dimers and a range of ICAM-1-coated particles to activated T cells. Lymphocyte function-associated antigen-1 (LFA-1) on the surface of activated T cells did not bind soluble ICAM-1 dimers with high affinity. In contrast, activated T cells adhered avidly to ICAM-1- coated planar surfaces. Between these two extremes, a range of ICAM-1- bearing particles was tested for binding. Activated T cells bound particles of 1-microm diameter or larger, but did not bind particles of 0.5-microm diameter or smaller. This threshold was eliminated, and all forms of ICAM-1 bound to LFA-1 when LFA-1 was converted to a high affinity form with an activating antibody. We show that high affinity LFA-1 is generated only as a consequence of an initial low affinity interaction of LFA-1 with ICAM-1 under physiological conditions. Therefore, the selectivity of cell surface LFA-1 for cell-sized particles bearing ICAM-1 appears to be due to the maintenance of low affinity LFA-1 on the surface of activated T cells. These findings alter the definition of inside-out signaling for LFA-1.

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