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 immu noglobulin gene superfamily, is a major ligand for the lymphocyte func tion-associated antigen 1 (LFA-1, CD18/CD11a) in the resting immune sy stem and plays a role as a signaling and costimulatory molecule on T l ymphocytes. 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 bindin g to recombinant chimeric ICAM-3-Fc proteins (which overcomes the conf ounding effects of interleukocyte LFA-1/ICAM binding events), we have been able to examine the effects of these antibodies in blocking LFA-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 el icit interleukin-2 production and cell proliferation in T lymphocytes.