TY - JOUR
T1 - Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells
AU - Giese, Madleen
AU - Turiello, Nadine
AU - Molenda, Nicole
AU - Palesch, David
AU - Meid, Annika
AU - Schroeder, Roman
AU - Basilico, Paola
AU - Benarafa, Charaf
AU - Halatsch, Marc-Eric
AU - Zimecki, Michal
AU - Westhoff, Mike-Andrew
AU - Wirtz, Christian Rainer
AU - Burster, Timo
PY - 2016/11/15
Y1 - 2016/11/15
N2 - Major histocompatibility complex (MHC) class I molecules present antigenic peptides to cytotoxic T cells. During an adaptive immune response, MHC molecules are regulated by several mechanisms including lipopolysaccharide (LPS) and interferon gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G (CatG), which is generally secreted by neutrophils at the site of inflammation, might regulate MHC I molecules. We identified CatG, and to a higher extend CatG and lactoferrin (LF), as an exogenous regulator of cell surface MHC I expression of immune cells and glioblastoma stem cells. In addition, levels of MHC I molecules are reduced on dendritic cells from CatG deficient mice compared to their wild type counterparts. Furthermore, cell surface CatG on immune cells, including T cells, B cells, and NK cells triggers MHC I on THP-1 monocytes suggesting a novel mechanism for CatG to facilitate intercellular communication between infiltrating cells and the respective target cell. Subsequently, our findings highlight the pivotal role of CatG as a checkpoint protease which might force target cells to display their intracellular MHC I:antigen repertoire.
AB - Major histocompatibility complex (MHC) class I molecules present antigenic peptides to cytotoxic T cells. During an adaptive immune response, MHC molecules are regulated by several mechanisms including lipopolysaccharide (LPS) and interferon gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G (CatG), which is generally secreted by neutrophils at the site of inflammation, might regulate MHC I molecules. We identified CatG, and to a higher extend CatG and lactoferrin (LF), as an exogenous regulator of cell surface MHC I expression of immune cells and glioblastoma stem cells. In addition, levels of MHC I molecules are reduced on dendritic cells from CatG deficient mice compared to their wild type counterparts. Furthermore, cell surface CatG on immune cells, including T cells, B cells, and NK cells triggers MHC I on THP-1 monocytes suggesting a novel mechanism for CatG to facilitate intercellular communication between infiltrating cells and the respective target cell. Subsequently, our findings highlight the pivotal role of CatG as a checkpoint protease which might force target cells to display their intracellular MHC I:antigen repertoire.
KW - Journal Article
U2 - 10.18632/oncotarget.12980
DO - 10.18632/oncotarget.12980
M3 - Article
C2 - 27806341
VL - 7
SP - 74602
EP - 74611
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 46
ER -