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cDNA clones encoding CD31 have been isolated by transient expression. The sequence of CD31 expressed on human umbilical vein endothelial cells (HUVEC) is identical to that expressed on the monocyte-like cell line HL60. In HUVEC. CD31 is concentrated in regions of cell-cell contacts. CD31 is a member of the Ig superfamily and is most closely related to the carcinoembryonic antigen CEA, consisting of four contiguous C2 domains. The localization of CD31 to regions of cell-cell contacts, and the sequence similarity to CEA, a known intercellular adhesion molecule (ICAM), strongly suggest that CD31 may function as an ICAM, possibly mediating endothelial cell-cell contacts and also promoting interactions between leukocytes and endothelial cells.