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, Timo Burster

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4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)74602-74611
Number of pages10
JournalOncotarget
Volume7
Issue number46
DOIs
Publication statusPublished - Nov 15 2016
Externally publishedYes

Keywords

  • Journal Article

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    Giese, M., Turiello, N., Molenda, N., Palesch, D., Meid, A., Schroeder, R., Basilico, P., Benarafa, C., Halatsch, M-E., Zimecki, M., Westhoff, M-A., Wirtz, C. R., & Burster, T. (2016). Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells. Oncotarget, 7(46), 74602-74611. https://doi.org/10.18632/oncotarget.12980