The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8 <sup>+</sup> T cells
Eliza Mari Kwesi‐Maliepaard, Muhammad Assad Aslam, Mir Farshid Alemdehy, Teun van den Brand, Chelsea McLean, Hanneke Vlaming, Tibor van Welsem, Tessy Korthout, Cesare Lancini, Sjoerd Hendriks, Tomasz Ahrends, Dieke van Dinther, Joke M. M. den Haan, Jannie Borst, Elzo de Wit, Fred van Leeuwen, Heinz Jacobs
Abstract
Significance Cytotoxic CD8 + T cells control infectious diseases as well as cancer. Memory T cells are a subset of CD8 + T cells that have previously encountered and rapidly responded to a specific antigen. Here we identified the epigenetic writer DOT1L as a central regulator of T cell physiology. In the absence of DOT1L, which methylates histone H3K79 at active genes, cytotoxic T cells prematurely acquired memory features without having encountered an antigen. However, loss of DOT1L in the T cell lineage led to a compromised immune response. Our findings highlight the importance of epigenetic signals in regulating T cell differentiation. Understanding these epigenetic signals is important for developing strategies to modulate T cell immunity.