Blood Advances (Oct 2019)
Identification of a tumor-specific allo-HLA–restricted γδTCR
- G.J.J. Kierkels,
- W. Scheper,
- A.D. Meringa,
- I. Johanna,
- D.X. Beringer,
- A. Janssen,
- M. Schiffler,
- T. Aarts-Riemens,
- L. Kramer,
- T. Straetemans,
- S. Heijhuurs,
- J.H.W. Leusen,
- E. San José,
- K. Fuchs,
- M. Griffioen,
- J.H. Falkenburg,
- L. Bongiovanni,
- A. de Bruin,
- D. Vargas-Diaz,
- M. Altelaar,
- A.J.R. Heck,
- L.D. Shultz,
- F. Ishikawa,
- M.I. Nishimura,
- Z. Sebestyén,
- J. Kuball
Affiliations
- G.J.J. Kierkels
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- W. Scheper
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- A.D. Meringa
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- I. Johanna
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- D.X. Beringer
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- A. Janssen
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- M. Schiffler
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- T. Aarts-Riemens
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- L. Kramer
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- T. Straetemans
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- S. Heijhuurs
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- J.H.W. Leusen
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- E. San José
- Facultad de Ciencias Biomédicas y Salud, Universidad Europea, Madrid, Spain;
- K. Fuchs
- Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands;
- M. Griffioen
- Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands;
- J.H. Falkenburg
- Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands;
- L. Bongiovanni
- Department of Pathobiology, Faculty of Veterinary Medicine, Dutch Molecular Pathology Center, Utrecht University, Utrecht, The Netherlands;
- A. de Bruin
- Department of Pathobiology, Faculty of Veterinary Medicine, Dutch Molecular Pathology Center, Utrecht University, Utrecht, The Netherlands;
- D. Vargas-Diaz
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;; Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
- M. Altelaar
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;; Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
- A.J.R. Heck
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;; Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
- L.D. Shultz
- Department of Immunology, The Jackson Laboratory, Bar Harbor, ME;
- F. Ishikawa
- Laboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan;
- M.I. Nishimura
- Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL
- Z. Sebestyén
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;
- J. Kuball
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;; Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; J. Kuball, UMC Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands;
- Journal volume & issue
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Vol. 3,
no. 19
pp. 2870 – 2882
Abstract
Abstract: γδT cells are key players in cancer immune surveillance because of their ability to recognize malignant transformed cells, which makes them promising therapeutic tools in the treatment of cancer. However, the biological mechanisms of how γδT-cell receptors (TCRs) interact with their ligands are poorly understood. Within this context, we describe the novel allo-HLA–restricted and CD8α-dependent Vγ5Vδ1TCR. In contrast to the previous assumption of the general allo-HLA reactivity of a minor fraction of γδTCRs, we show that classic anti-HLA–directed, γδTCR-mediated reactivity can selectively act on hematological and solid tumor cells, while not harming healthy tissues in vitro and in vivo. We identified the molecular interface with proximity to the peptide-binding groove of HLA-A*24:02 as the essential determinant for recognition and describe the critical role of CD8 as a coreceptor. We conclude that alloreactive γδT-cell repertoires provide therapeutic opportunities, either within the context of haplotransplantation or as individual γδTCRs for genetic engineering of tumor-reactive T cells.
