Using a cDNA subtraction technique, a novel member of the ubiquitin family was isolated from human dendritic cells. This gene encodes a diubiquitin protein containing tandem head to tail ubiquitin-like domains, with the conservation of key functional residues. Expression of this 777-bp mRNA was restricted to dendritic cells and B cells, with strong expression in mature B cells. Southern blot analysis indicated that a single copy of this gene is present. In situ hybridization on tonsillar tissue showed expression in epithelial cells and isolated cells within the germinal center. With respect to an expressed-sequence tag (EST) this cDNA could be localized to the major histocompatibility complex class I region of chromosome 6. Comparative analysis and the expression pattern of this gene suggests a function in antigen processing and presentation.