Presentation and intercellular transfer of self antigen within the thymic microenvironment: expression of the Eα peptide-l-Ab complex by isolated thymic stromal cells

Abstract

Expression of a self peptlde derived from the α chain of MHC class II (I-E^d) in association with I-A^b was studied in the murine thymic microenvironment Previous work using the mAb Y-Ae which specifically recognizes the Eα-A^b complex had reported differential expression between the thymic medulla and the cortex of this peptide-MHC complex: MHC class 11-positive stromal cells in the medulla were strongly positive, whereas this complex was barely detectable on cortical epithelial cells (cEpC) in situ. This difference in presentation of an abundant self peptlde is intriguing, since the self protein from which this peptlde is derived and the presenting MHC molecule are strongly expressed in both compartments. In this report we show by cell surface phenotype and functional assays that isolated cEpC express the Eα-l-A^b complex at significant although lower levels than medullary dendritic cells (DC), when examined ex vivo. These results support the notion that cEpC and bone marrow-derived stromal cells present a similar set of self peptide-MHC complexes in situ. In addition, we detect intercellular transfer in situ of the Eα determinant from radioresistant stromal cells to thymic DC, a mechanism which may enhance the efficacy of tolerance induction by spreading self antigens within the thymic microenvironment