TY - JOUR T1 - A genome-wide innateness gradient defines the functional state of human innate T cells JF - bioRxiv DO - 10.1101/280370 SP - 280370 AU - M. Gutierrez-Arcelus AU - N. Teslovich AU - A. R. Mola AU - H. Kim AU - S. Hannes AU - K. Slowikowski AU - G. F. M. Watts AU - M. Brenner AU - S. Raychaudhuri AU - P. J. Brennan Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/03/13/280370.abstract N2 - Innate T cells (ITCs), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cell populations, use conserved antigen receptors generated by somatic recombination to respond to non-peptide antigens in an innate-like manner. Understanding where these cells fit in the scheme of immunity has been a puzzle since their discovery. Here, immunophenotyping of 101 individuals revealed that these populations account for as much as 25% of peripheral human T cells. To better understand these cells, we generated detailed gene expression profiles using low-input RNA-seq and confirmed key findings through protein-level and functional validation. Unbiased transcriptomic analyses revealed a continuous ‘innateness gradient’ with adaptive T cells at one end followed by MAIT, iNKT, Vδ1+ T, Vδ2+ T, and natural killer cells at the other end. Innateness was characterized by decreased expression of translational machinery genes and reduced proliferative potential, which allowed for prioritization of effector functions, including rapid cytokine and chemokine production, and cytotoxicity. Thus, global transcriptional programs uncovered rapid proliferation and rapid effector functions as competing goals that respectively define adaptive and innate states.One Sentence Summary Adaptive and innate T cells align along a continuous innateness gradient, reflecting a trade-off between effector function and proliferative capacity. ER -