CLONING, MAPPING, AND CHARACTERIZATION OF ACTIVATED LEUKOCYTE-CELL ADHESION MOLECULE (ALCAM), A CD6 LIGAND

Antibody-blocking studies have demonstrated the role of CD6 in thymocy te-thymic epithelial (TE) cell adhesion. Here we report that CD6 expre ssed by COS cells mediates adhesion to TE cells and that this interact ion is specifically blocked with an anti-CD6 monoclonal antibody (mAb) or with a mAb (J4-81) that recognized a TE cell antigen. We isolated and expressed a cDNA clone encoding this antigen and show that COS cel ls transfected with this cDNA bind a CD6 immunoglobulin fusion protein (CD6-Rg). This antigen, which we named ALCAM (activated leukocyte-cel l adhesion molecule) because of its expression on activated leukocytes , appears to be the human homologue of the chicken neural adhesion mol ecule BEN/SC-1/DM-GRASP. The gene was mapped to human chromosome 3q13. 1-q13.2 by fluorescence in situ hybridization of cDNA probes to metaph ase chromosomes. We prepared an ALCAM-Rg fusion protein and showed tha t it binds to COS cell transfectants expressing CD6, demonstrating tha t ALCAM is a CD6 ligand. The observations that ALCAM is also expressed by activated leukocytes and that both ALCAM and CD6 are expressed in the brain suggest that ALCAM-CD6 interactions may play a role in the b inding of T and B cells to activated leukocytes, as well as in interac tions between cells of the nervous system.