The NF-κB transcription factor RelA directs mucosal-associated invariant T-cell development

Mucosal-associated invariant T (MAIT) cells are characterized by rapid responses to nonpeptide antigens via invariant T-cell receptors (TCR), and expression of an “effector-like” T-cell phenotype. The transcription factor promyelocytic leukemia zinc finger (PLZF) is crucial for defining the function of MAIT cells and other unconventional T cells; however, the transcriptional programs that direct MAIT cell development are not fully elucidated. Here, we show that the canonical NF-κB transcription factor RelA is critical for MAIT cell thymic development, but not responsiveness to antigen, whereas NF-κB1 and c-Rel make more limited contributions. MAIT cell development is also impaired in the absence of the linear ubiquitin signaling complex (LUBAC), an upstream regulator of NF-κB signaling, implicating this pathway in establishing the MAIT cell pool. Collectively, these data suggest LUBAC and NF-κB signals as elements of the transcriptional network controlling MAIT cell development.