Oncotarget

Research Papers: Immunology:

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

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 and Timo Burster _

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Oncotarget. 2016; 7:74602-74611. https://doi.org/10.18632/oncotarget.12980

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Abstract

Madleen Giese1, Nadine Turiello1, Nicole Molenda1, David Palesch2, Annika Meid1, Roman Schroeder1, Paola Basilico3,4, Charaf Benarafa3, Marc-Eric Halatsch1, Michal Zimecki5, Mike-Andrew Westhoff6, Christian Rainer Wirtz1 and Timo Burster1

1 Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany

2 Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany

3 Theodor Kocher Institute, University of Bern, Bern, Switzerland

4 Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland

5 Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

6 Department Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany

Correspondence to:

Timo Burster, email:

Keywords: cathepsin G, MHC class I, glioblastoma stem cells, lactoferrin, CatG deficient mice, Immunology and Microbiology Section, Immune response, Immunity

Received: April 28, 2016 Accepted: October 25, 2016 Published: October 28, 2016

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.


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