THE LW BLOOD-GROUP GLYCOPROTEIN IS HOMOLOGOUS TO INTERCELLULAR-ADHESION MOLECULES

The LW blood group antigens reside on a 42-kDa erythrocyte membrane gl ycoprotein that was purified by immunoaffinity and partially sequenced . From this information, a specific PCR-amplified DNA fragment was use d to screen a lambda gt11 human bone marrow cDNA library. Two forms of cDNA were isolated; the first encoded a single spanning transmembrane protein of 270 amino acids, including a 29-amino acid peptide signal and four potential N-glycosylation sites, and the second encoded a sho rtened protein form of 236 residues devoid of transmembrane and cytopl asm domains. A rabbit antibody raised against the 15 N-terminal amino acids of the predicted protein reacted on immunoblots with authentic L W glycoprotein and in indirect agglutination test with all human eryth rocytes except those from LW(a-b-). This showed that the protein encod ed by these clones was LW gene product and suggested that the N termin us of the LW protein is oriented extracellularly. Most interestingly, the LW protein was found to exhibit sequence similarities (with approx imate to 30% identity) with intercellular adhesion molecules ICAM-1, - 2, and -3, which are the counterreceptors for the lymphocyte function- associated antigens LFA-1. The extracellular domain of LW consists, li ke that of ICAM-2, of two immunoglobulin-like domains, and the critica l residues involved in the binding of LFA-I to ICAMs were partially co nserved in LW.