Cathepsin L: Critical Role in Ii Degradation and CD4 T Cell Selection in the Thymus

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Science  17 Apr 1998:
Vol. 280, Issue 5362, pp. 450-453
DOI: 10.1126/science.280.5362.450

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Degradation of invariant chain (Ii) is a critical step in major histocompatibility complex class II–restricted antigen presentation. Cathepsin L was found to be necessary for Ii degradation in cortical thymic epithelial cells (cTECs), but not in bone marrow (BM)–derived antigen-presenting cells (APCs). Consequently, positive selection of CD4+ T cells was reduced. Because different cysteine proteinases are responsible for specific Ii degradation steps in cTECs and BM-derived APCs, the proteolytic environment in cells mediating positive and negative selection may be distinct. The identification of a protease involved in class II presentation in a tissue-specific manner suggests a potential means of manipulating CD4+ T cell responsiveness in vivo.

  • * These authors contributed equally to this work.

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