A key ingredient for priming killer T cells
Menée à l'aide de modèles murins, cette étude met notamment en évidence le rôle joué par la protéine WDFY4 dans l'immunité antitumorale
For the adaptive immune system to detect intracellular infection, microbial protein fragments (antigens) must be presented by major histocompatibility complex class I (MHC-I) molecules. This entails an elaborate intracellular folding of MHC-I molecules with peptides from the infecting pathogen, followed by their display on the cell surface for surveillance by CD8+ T cells (1). In a variation of this classical pathway of MHC-I antigen presentation, a subset of professional antigen-presenting cells called dendritic cells (DCs) conduct cross-presentation, whereby MHC-I molecules are directed to present exogenous peptides from internalized microbes and dying infected cells or cancer cells (2). Because of the potential to prime cytotoxic CD8+ T cells against intracellular pathogens and cancer cells, cross-presentation has preoccupied immunologists for decades. But how this process is orchestrated remains poorly understood. On page 694 of this issue, Theisen et al. (3) reveal a critical role for the protein WDFY4 (WD repeat- and FYVE domain–containing protein 4) in cross-presentation and not in classical MHC-I antigen presentation. The authors show that WDFY4 works specifically in the conventional DC1 (cDC1) subset and is responsible for their specialization at cross-presentation (4). This revelation identifies WDFY4 as a therapeutic target to mobilize cytotoxic CD8+ T cells against tumors and infected cells.
Science 2018