Epitope mapping and functional properties of anti‐intercellular adhesion molecule‐3 (CD50) monoclonal antibodies

Intercellular adhesion molecule‐3 (ICAM‐3, CD50), a member of the immunoglobulin gene superfamily, is a major ligand for the lymphocyte functionassociated antigen 1 (LFA‐1, CD18/CD11a) in the resting immune system and plays a role as a signaling and costimulatory molecule on T lymphocytes. In this study we have generated a large panel of anti‐ICAM‐3 monoclonal antibodies (mAb) and show that the biological effects of these antibodies are critically dependent on the epitope recognized. By using an adhesion assay employing COS cells expressing LFA‐1 binding to recombinant chimeric ICAM‐3‐Fc proteins (which overcomes the confounding effects of interleukocyte LFA‐1/ICAM binding events), we have been able to examine the effects of these antibodies in blocking IFA‐1/ICAM‐3 adhesion. Our data suggests that only a small minority of ICAM‐3 mAb, recognizing a distinct epitope, are able to mimic the effects of LFA‐1 binding to ICAM‐3. Moreover these antibodies are functionally distinct as defined by their costimulatory activity and ability to elicit interleukin‐2 production and cell proliferation in T lymphocytes.