Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells.

Abstract

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.

• Authors: Madleen Giese, Nadine Turiello, Nicole Molenda, David Palesch, Annika Meid, Roman Schroeder, Paola Basilico, Charaf Benarafa, Marc-Eric Halatsch, Michal Zimecki, Mike-Andrew Westhoff, Christian Rainer Wirtz, Timo Burster
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 46 Pg. 74602-74611 (Nov 15 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27806341 (Publication Type: Journal Article)

Chemical References

• Histocompatibility Antigens Class I
• Lactoferrin
• Cathepsin G

Topics

• Animals
• Cathepsin G (genetics, metabolism, pharmacology)
• Cell Line
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Disease Models, Animal
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioblastoma (genetics, immunology, metabolism)
• Histocompatibility Antigens Class I (genetics, metabolism)
• Humans
• Immune System (cytology, immunology, metabolism)
• Lactoferrin (metabolism)
• Male
• Mice
• Mice, Knockout
• Monocytes (drug effects, metabolism)
• Neoplastic Stem Cells (drug effects, metabolism)
• Proteolysis