HLA-DO is an intracellular class II molecule with distinctive thymic expression

The status of the HLA-DNA and -DOB genes in the HLA class II region has remained unclear for several years. Weak mRNA transcripts from each locus can be detected in B cells and some other cell types, but the issues of whether proteins are generated and, if so, whether they acquire partner chains to form class II heterodimers have not been resolved. The products of the homologous murine genes pair with each other to form the H-20 heterodimer. We now report that the products of HLA-DNA and -DOB are expressed as a heterodimer in humans, HLA-DO. It is expressed in various class II-positive cells including dendritic cells. The heterodimer associates with invariant chain and has a relatively short half-life. Its subcellular distribution differs from HLA-DR such that it is not expressed at the cell surface although it is found in some DR-containing compartments, suggesting a role at the intracellular stage of class II function. In the thymus, subpopulations of cells in both cortex and medulla, including HLA-DR(+) and DR(-) cells, are HLA-DO+. Hassall's corpuscles, a medullary site of thymocyte death, are ringed by HLA-DO+ epithelium. This unusual pattern of expression may suggest a specialized role for HLA-DO in the thymus.