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The Ubiquitin Ligase Adaptor NDFIP1 Selectively Enforces a CD8+ T Cell Tolerance Checkpoint to High-Dose Antigen

Wagle, Mayura V; Marchingo, Julia M; Howitt, Jason; Tan, Seong-Seng; Goodnow, Christopher C; Parish, Ian A


Escape from peripheral tolerance checkpoints that control cytotoxic CD8+ T cells is important for cancer immunotherapy and autoimmunity, but pathways enforcing these checkpoints are mostly uncharted. We reveal that the HECT-type ubiquitin ligase activator, NDFIP1, enforces a cell-intrinsic CD8+ T cell checkpoint that desensitizes TCR signaling during in vivo exposure to high antigen levels. Ndfip1-deficient OT-I CD8+ T cells responding to high exogenous tolerogenic antigen doses that normally...[Show more]

CollectionsANU Research Publications
Date published: 2018-07-17
Type: Journal article
Source: Cell reports
DOI: 10.1016/j.celrep.2018.06.060
Access Rights: Open Access


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