The LW blood group glycoprotein is homologous to intercellular adhesion molecules

Abstract

The LW blood group antigens reside on a 42-kDa erythrocyte membrane glycoprotein that was purified by immunoaffinity and partiafly sequenced. From this information, a specific PCR-amplifled DNA fragment was used to screen a Agtll human bone marrow cDNA library. LW(a-b-). This showed that the protein encoded by these clones was LW gene product and suggested that the N terminus of the LW protein is oriented extracellularly. Most interestingly, the LW protein was found to exhibit sequence similarities (with -30% identity) with intercellular adhesion molecules ICAM-1, -2, and -3, which are the counterreceptors for the lymphocyte functionassociated antigens LFA-1. The extraceflular domain of LW consists, like that of ICAM-2, of two immunoglobulin-like doins, and the critical residues involved in the binding of LFA-1 to ICAMs were partially conserved in LW.The LW and Rh (rhesus) blood group systems were discovered simultaneously and were confused for a long time (reviews, refs. 1-3 Affinity Purification of the LW Protein. Membranes from two units of LW(a+b-) red cells were solubilized with 1% (wt/vol) Triton X-100 in phosphate-buffered saline (PBS) and applied to a specific affinity matrix column, prepared by binding 9 mg of purified murine monoclonal IgG antibody anti-LW (BS46) to 2 ml of protein A-agarose followed by cross-linking of the complex with dimethylpimelimidate (ImmunoPure IgG orientation kit, Pierce). After washing, the LW antigenic material bound was eluted with a glycine buffer (pH 2.8) and immediately brought to near neutrality.