GILT in thymic epithelial cells preferentially facilitates MHC class II-restricted presentation in generating central T cell tolerance to a self and melanoma antigen

• DOI: 10.4049/jimmunol.200.supp.165.17
• Publication Date: 2023-01-02T03:18:50Z
• Authors: Lydia Meador; Matthew P Rausch; Todd C Metzger; Mark S Anderson; Karen Taraszka Ha...
• Keywords: Central tolerance; Antigen processing; Peripheral tolerance; MHC restriction

Abstract Central tolerance prevents autoimmunity, but limits T cell responses to tumor antigens that are self antigens. In peripheral APCs, gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of disulfide bond-containing proteins, including the and melanoma antigen tyrosinase-related protein 1 (TRP1). The role GILT in thymic processing generation central unknown. We found enhanced clonal deletion TRP1-specific thymocytes. expression was enriched APCs capable mediating deletion, namely medullary epithelial cells (mTECs) dendritic cells. TRP1 restricted mTECs. facilitated endogenous by pooled APCs. Using bone marrow chimeras, (TECs), not hematopoietic cells, sufficient Chimeras with TECs also had an increased frequency regulatory (Treg) These data demonstrate advantage TEC-derived subsequent tolerance. Only chimeras lacked both were protected from a high effector cell:Treg ratio. Thus, diminishes cell-mediated protection through promoting Treg