Frontiers in Immunology (Jul 2018)
Anti-CD3 Fab Fragments Enhance Tumor Killing by Human γδ T Cells Independent of Nck Recruitment to the γδ T Cell Antigen Receptor
- Claudia Juraske,
- Claudia Juraske,
- Claudia Juraske,
- Piyamaporn Wipa,
- Piyamaporn Wipa,
- Piyamaporn Wipa,
- Anna Morath,
- Anna Morath,
- Anna Morath,
- Anna Morath,
- Jose Villacorta Hidalgo,
- Jose Villacorta Hidalgo,
- Frederike A. Hartl,
- Frederike A. Hartl,
- Frederike A. Hartl,
- Katrin Raute,
- Katrin Raute,
- Katrin Raute,
- Katrin Raute,
- Hans-Heinrich Oberg,
- Daniela Wesch,
- Paul Fisch,
- Susana Minguet,
- Susana Minguet,
- Susana Minguet,
- Sutatip Pongcharoen,
- Sutatip Pongcharoen,
- Sutatip Pongcharoen,
- Wolfgang W. Schamel,
- Wolfgang W. Schamel,
- Wolfgang W. Schamel
Affiliations
- Claudia Juraske
- Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Claudia Juraske
- Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany
- Claudia Juraske
- Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Piyamaporn Wipa
- Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Piyamaporn Wipa
- Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany
- Piyamaporn Wipa
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
- Anna Morath
- Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Anna Morath
- Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany
- Anna Morath
- Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Anna Morath
- Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany
- Jose Villacorta Hidalgo
- Department of Pathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Jose Villacorta Hidalgo
- University Hospital “José de San Martin”, University of Buenos Aires, Buenos Aires, Argentina
- Frederike A. Hartl
- Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Frederike A. Hartl
- Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany
- Frederike A. Hartl
- Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Katrin Raute
- Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Katrin Raute
- Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany
- Katrin Raute
- Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Katrin Raute
- Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany
- Hans-Heinrich Oberg
- Institute of Immunology, Christian-Albrechts University of Kiel, Kiel, Germany
- Daniela Wesch
- Institute of Immunology, Christian-Albrechts University of Kiel, Kiel, Germany
- Paul Fisch
- Department of Pathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Susana Minguet
- Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Susana Minguet
- Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany
- Susana Minguet
- Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Sutatip Pongcharoen
- Division of Immunology, Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok, Thailand
- Sutatip Pongcharoen
- 0Research Center for Academic Excellence in Petroleum, Petrochemical and Advanced Materials, Faculty of Science, Naresuan University, Phitsanulok, Thailand
- Sutatip Pongcharoen
- 1Centre of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
- Wolfgang W. Schamel
- Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Wolfgang W. Schamel
- Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany
- Wolfgang W. Schamel
- Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- DOI
- https://doi.org/10.3389/fimmu.2018.01579
- Journal volume & issue
-
Vol. 9
Abstract
T lymphocytes expressing the γδ T cell receptor (γδ TCR) can recognize antigens expressed by tumor cells and subsequently kill these cells. γδ T cells are indeed used in cancer immunotherapy clinical trials. The anti-CD3ε antibody UCHT1 enhanced the in vitro tumor killing activity of human γδ T cells by an unknown molecular mechanism. Here, we demonstrate that Fab fragments of UCHT1, which only bind monovalently to the γδ TCR, also enhanced tumor killing by expanded human Vγ9Vδ2 γδ T cells or pan-γδ T cells of the peripheral blood. The Fab fragments induced Nck recruitment to the γδ TCR, suggesting that they stabilized the γδ TCR in an active CD3ε conformation. However, blocking the Nck-CD3ε interaction in γδ T cells using the small molecule inhibitor AX-024 neither reduced the γδ T cells’ natural nor the Fab-enhanced tumor killing activity. Likewise, Nck recruitment to CD3ε was not required for intracellular signaling, CD69 and CD25 up-regulation, or cytokine secretion by γδ T cells. Thus, the Nck-CD3ε interaction seems to be dispensable in γδ T cells.
Keywords
