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Positive selection and the generation of a ‘useful’ T cell repertoire

Positive selection requires permissive interactions with a single antigen presenting cell (APC) type, namely cortical thymic epithelial cells (cTECs). Why positive selection depends on a single stromal cell type remains a conundrum, but it is becoming increasingly clear that the crucial role of cTECs is, at least in part, specified by unique machineries that these cells use to generate pMHC ligands. These proteolytic pathways are likely to endow cTECs with an at least in part ‘private’ self-peptide/major histocompatibility complex (pMHC) ligandome different from that on other APCs. In this context, we are addressing how the cTEC specific protease Cathepsin L shapes the CD4 T cell repertoire and imprints the functional competence of mature T cells.