Abstract
THE repertoire of receptors expressed by peripheral T cells is the result of two selective events that occur during intrathymic development. Positive selection expands cells able to recognize foreign peptides presented by self MHC molecules, and negative selection eliminates cells reactive to self MHC molecules and associated self peptides1–4. Chimaera studies suggest that, at least in the case of T cells recognizing MHC class II, interaction with thymic cortical epithelial cells is responsible for the former5, whereas thymic medullary cells, of bone marrow origin, mediate the latter3, 6–8. This view of thymic development is supported by recent morphometric analyses9, showing that autoreactive cells are found in thymic cortex but not medulla. Although numerous1–3, 10–12 studies have shown that MHC class II molecules are expressed in both sites, none provides any explanation for the differential selection of T cells that is observed. Here, we describe a novel MHC class II epitope which is found on cells in thymic medulla but not cortex. The antibody to this epitope reacts with about 10% of class II molecules on B cells and may be recognizing a self peptide–MHC complex. These results provide the first evidence for differential expression of class II epitopes in different tissues and are compatible with the hypothesis that different ligands2, 13–16, rather than different affinity thresholds for the same ligand17, 18, are involved in positive and negative selection of the T-cell repertoire.
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Murphy, D., Lo, D., Rath, S. et al. A novel MHC class II epitope expressed in thymic medulla but not cortex. Nature 338, 765–768 (1989). https://doi.org/10.1038/338765a0
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DOI: https://doi.org/10.1038/338765a0
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