Intercellular adhesion molecule-3 (ICAM-3, CD50), a member of the immunoglobulin 
gene superfamily, is a major ligand for the lymphocyte function-associated 
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 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 elicit interleukin-2 production and 
cell proliferation in T lymphocytes.