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 ha s remained unclear for several years. Weak mRNA transcripts from each locus can be detected in B cells and some other cell types, but the is sues of whether proteins are generated and, if so, whether they acquir e partner chains to form class II heterodimers have not been resolved. The products of the homologous murine genes pair with each other to f orm the H-20 heterodimer. We now report that the products of HLA-DNA a nd -DOB are expressed as a heterodimer in humans, HLA-DO. It is expres sed 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 sta ge of class II function. In the thymus, subpopulations of cells in bot h cortex and medulla, including HLA-DR(+) and DR(-) cells, are HLA-DO. Hassall's corpuscles, a medullary site of thymocyte death, are ringe d by HLA-DO+ epithelium. This unusual pattern of expression may sugges t a specialized role for HLA-DO in the thymus.