Distinct binding of T lymphocytes to ICAM‐1, ‐2 or ‐3 upon activation of LFA‐1

Abstract

LFA‐1 (CD11a/CD18) mediates leukocyte adhesion by binding to one of its ligands: ICAM‐1, ICAM‐2 or ICAM‐3. Here, we investigated whether stimuli known to induce adhesion to ICAM‐1 were also capable of inducing LFA‐1‐mediated adhesion of T lymphocytes to ICAM‐2 and ‐3 transfectants. We observed that phorbol 12‐myristate 13‐acetate, Mn²⁺, cross‐linking of CD3 or activating antibodies against LFA‐1 enhanced LFA‐1‐mediated T cell adhesion to ICAM‐2 and ‐3, although to a lesser extent than to ICAM‐1. These results indicate that, similar to what has been reported for adhesion to ICAM‐1, activation of LFA‐1 is also required for adhesion to ICAM‐2 and ‐3. Furthermore, the results suggest that ICAM‐1 is the major ligand for LFA‐1 on activated T lymphocytes. Interestingly, we observed that in contrast to activating antibodies against CD18, activating antibodies against CD11a were incapable of inducing adhesion of LFA‐1 to all three ligands. The antibody MEM‐83 stimulated binding to ICAM‐1, while at the same time inhibiting the interaction of LFA‐1 with ICAM‐2 and ‐3. The antibody NKI‐L16 selectively induced adhesion to ICAM‐1 and ‐2, but not to ICAM‐3. Our results suggest that different conformations of LFA‐1 are required to support adhesion to ICAM‐1, ‐2 or ‐3, and that ligands may bind on different sites of the LFA‐1 molecule.