Cloning and characterization of a new intercellular adhesion molecule ICAM-R

Abstract

THE human intercellular adhesion molecules ICAM-1, 1C AM-2 and their counter-receptors, the β₂ or leukointegrins, mediate a variety of homotypic and heterotypic leukocyte and endothelial cell–cell adhesions central to immunocompetence¹. It has been found² that cell–cell adhesion which is dependent on expression of the leukocyte function-associated antigen LFA-1 is not always blocked completely by antibodies raised against ICAM-1 and I CAM-2. Other leukointegrin ligands therefore probably exist, such as a glycoprotein of M_r 124K that binds LFA-1 and has been designated ICAM-3 on the basis of this function³. We have molecularly cloned a new member of the ICAM family, ICAM-R, which is related to ICAM-1 and ICAM-2. The complementary DNA encoding ICAM-R is 1,781 base pairs long and the protein has five extracellular immunoglobulin-family type domains. The mature cell-surface form of the ICAM-R protein has an M_r which varies from 116 to 140K in a cell type-specific fashion. Overall identities in protein sequence with ICAM-1 and ICAM-2 are 48% and 31% respectively, with the degree of similarity varying between individual domains. The high level of expression of ICAM-R on resting leukocytes of all lineages and its lack of expression on either resting or cytokine-activated endothelial cells indicates a pattern of expression distinct from ICAM-1 and ICAM-2. In common with ICAM-1 and ICAM-2, ICAM-R is a ligand for the β₂-integrin CDlla/LFA-1 (CD18).