LOW-AFFINITY OF CELL-SURFACE LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1(LFA-1) GENERATES SELECTIVITY FOR CELL-CELL INTERACTIONS

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 a ctivated T cells did not bind soluble ICAM-1 dimers with high affinity , In contrast, activated T cells adhered avidly to ICAM-1-coated plana r surfaces. Between these two extremes, a range of ICAM-1-bearing part icles was tested for binding. Activated T cells bound particles of 1-m u m diameter or larger, but did not bind particles of 0.5-mu m diamete r or smaller. This threshold was eliminated, and all forms of ICAM-1 b ound 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 on ly as a consequence of an initial low affinity interaction of LFA-1 wi th ICAM-1 under physiological conditions, Therefore, the selectivity o f cell surface LFA-1 for cell-sized particles bearing ICAM-1 appears t o be due to the maintenance of low affinity LFA-1 on the surface of ac tivated T cells. These findings alter the definition of inside-out sig naling for LFA-1. We examined binding of soluble intercellular adhesio n molecule-1 (ICAM-1) dimers and a range of ICAM-1-coated particles to activated T cells. Lymphocyte function-associated antigen-1 (LFA-1) o n the surface of activated T cells did not bind soluble ICAM-1 dimers with high affinity, In contrast, activated T cells adhered avidly to I CAM-1-coated planar surfaces. Between these two extremes, a range of I CAM-1-bearing particles was tested for binding. Activated T cells boun d particles of 1-mu m diameter or larger, but did not bind particles o f 0.5-mu m 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 aff inity form with an activating antibody. We show that high affinity LFA -1 is generated only as a consequence of an initial low affinity inter action of LFA-1 with ICAM-1 under physiological conditions, Therefore, the selectivity of cell surface LFA-1 for cell-sized particles bearin g 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.