THE CD39 LYMPHOID-CELL ACTIVATION ANTIGEN - MOLECULAR-CLONING AND STRUCTURAL CHARACTERIZATION

CD39, a 70- to 100-kDa molecule expressed primarily on activated lymph oid cells, was previously shown to mediate B cell homotypic adhesion w hen ligated with a subset of anti-CD39 mAbs. In the present study, we describe the cloning and molecular characterization of human and murin e CD39. The nucleotide sequence of human CD39 includes an open reading frame encoding a putative 510 amino acid protein with six potential N -linked glycosylation sites, 11 Cys residues, and two potential transm embrane regions. Murine CD39 shares 75% amino acid sequence identity w ith human CD39 but fails to cross-react with anti-human CD39 mAbs. Alt hough there were no significant similarities with other mammalian gene s, considerable homology was found between CD39 and a guanosine diphos phatase from yeast. A series of mouse-human hybrid molecules was const ructed to determine the general topology of CD39 and the location of a biologically functional epitope. These findings and supporting eviden ce from an anti-CD39 mAb-selected phage peptide display library indica te a likely model wherein a short intracellular N-terminus is followed by a large extracellular loop containing the epitope recognized by st imulatory anti-CD39 mAbs, and a short intracellular C terminus. The re sults demonstrate that CD39 is a novel cell surface glycoprotein with unusual structural characteristics.