Аннотация:
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