Restricted expression of transgenic HLA‐DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self‐superantigens and processed DRα‐derived peptide

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Abstract
We have established a set of transgenic mouse lines in which the HLA‐DRA gene was expressed in different cell types. In one line (DRα‐24), DRαEβb molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow‐derived antigen‐presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DRα‐30) was found on thymic medullary and cortical epithelial cells but not on bone marrow‐derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DRα‐24 and DRα‐30 was performed. In DRα‐30, T cells expressing TcR Vβ5 and Vβ11 were eliminated to comparable levels to those in DRα‐24, suggesting that expression of the DRαEβb molecules on thymic epithelial cells are sufficient for clonal deletion of the self‐superantigen‐reactive T cells. In addition, CD4+ T cells from DRa‐30 as well as those from DRα‐24 were tolerant to DRα‐derived peptide/I‐Ab complex expressed on spleen cells from DRα‐24 even in the presence of exogenous interleukin‐2. These observations suggest that expression of the DRα chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DRα‐derived peptide bound to I‐Ab molecules, probably via clonal deletion of the self‐reactive T cells.