| First Author | Wagle MV | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 3 | Pages | 577-584 |
| PubMed ID | 30021156 | Mgi Jnum | J:270847 |
| Mgi Id | MGI:6278786 | Doi | 10.1016/j.celrep.2018.06.060 |
| Citation | Wagle MV, et al. (2018) The Ubiquitin Ligase Adaptor NDFIP1 Selectively Enforces a CD8(+) T Cell Tolerance Checkpoint to High-Dose Antigen. Cell Rep 24(3):577-584 |
| abstractText | 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 induce anergy aberrantly expanded and differentiated into effector cells that could precipitate autoimmune diabetes in RIP-OVA(hi) mice. In contrast, NDFIP1 was dispensable for peripheral deletion to low-dose exogenous or pancreatic islet-derived antigen and had little impact upon effector responses to Listeria or acute LCMV infection. These data provide evidence that NDFIP1 mediates a CD8(+) T cell tolerance checkpoint, with a different mechanism to CD4(+) T cells, and indicates that CD8(+) T cell deletion and anergy are molecularly separable checkpoints. |
