TCR-Ligand koff Rate Correlates with the Protective Capacity of Antigen-Specific CD8+ T Cells for Adoptive Transfer

Magdalena Nauerth; Bianca Weißbrich; Robert Knall; Tobias Franz; Georg Dössinger; Jeannette Bet; Paulina J. Paszkiewicz; Lukas Pfeifer; Mario Bunse; Wolfgang Uckert; Rafaela Holtappels; Dorothea Gillert-Marien; Michael Neuenhahn; Angela Krackhardt; Matthias J. Reddehase; Stanley R. Riddell; Dirk H. Busch

doi:10.1126/scitranslmed.3005958

Research ArticleImmunology

TCR-Ligand k_off Rate Correlates with the Protective Capacity of Antigen-Specific CD8⁺ T Cells for Adoptive Transfer

Magdalena Nauerth¹,*,
Bianca Weißbrich¹,*,
Robert Knall¹,*,
Tobias Franz¹,
Georg Dössinger¹,
Jeannette Bet¹,²,
Paulina J. Paszkiewicz¹,²,
Lukas Pfeifer¹,
Mario Bunse³,⁴,
Wolfgang Uckert³,⁴,
Rafaela Holtappels⁵,
Dorothea Gillert-Marien⁵,
Michael Neuenhahn¹,⁶,⁷,
Angela Krackhardt⁶,⁸,
Matthias J. Reddehase⁵,⁹,
Stanley R. Riddell²,¹⁰,¹¹ and
Dirk H. Busch¹,²,⁶,⁷,†

¹Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.
²Focus Group “Clinical Cell Processing and Purification,” Institute for Advanced Study, Technische Universität München, 81675 Munich, Germany.
³Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
⁴Humboldt-Universität Berlin, 10099 Berlin, Germany.
⁵Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.
⁶Clinical Cooperation Groups “Antigen-specific Immunotherapy” and “Immune Monitoring,” Helmholtz Center Munich (85764 Neuherberg) and Technische Universität München, 81675 Munich, Germany.
⁷DZIF–National Centre for Infection Research, 81675 Munich, Germany.
⁸Medical Department III, Hematology and Oncology, Technische Universität München, 81675 Munich, Germany.
⁹Helmholtz Virtual Institute on Viral Strategies of Immune Evasion (VISTRIE), Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
¹⁰Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
¹¹Department of Medicine, University of Washington, Seattle, WA 98104, USA.

↵†Corresponding author. E-mail: dirk.busch{at}mikrobio.med.tum.de

↵* These authors contributed equally to this work.

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Science Translational Medicine 03 Jul 2013:
Vol. 5, Issue 192, pp. 192ra87
DOI: 10.1126/scitranslmed.3005958

Magdalena Nauerth

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.

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Bianca Weißbrich

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.

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Robert Knall

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.

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Tobias Franz

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.

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Georg Dössinger

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.

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Jeannette Bet

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Paulina J. Paszkiewicz

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Lukas Pfeifer

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.

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Mario Bunse

Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.Humboldt-Universität Berlin, 10099 Berlin, Germany.

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Wolfgang Uckert

Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.Humboldt-Universität Berlin, 10099 Berlin, Germany.

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Rafaela Holtappels

Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.

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Dorothea Gillert-Marien

Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.

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Michael Neuenhahn

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.Clinical Cooperation Groups “Antigen-specific Immunotherapy” and “Immune Monitoring,” Helmholtz Center Munich (85764 Neuherberg) and Technische Universität München, 81675 Munich, Germany.DZIF–National Centre for Infection Research, 81675 Munich, Germany.

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Angela Krackhardt

Clinical Cooperation Groups “Antigen-specific Immunotherapy” and “Immune Monitoring,” Helmholtz Center Munich (85764 Neuherberg) and Technische Universität München, 81675 Munich, Germany.Medical Department III, Hematology and Oncology, Technische Universität München, 81675 Munich, Germany.

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Matthias J. Reddehase

Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.Helmholtz Virtual Institute on Viral Strategies of Immune Evasion (VISTRIE), Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.

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Stanley R. Riddell

Focus Group “Clinical Cell Processing and Purification,” Institute for Advanced Study, Technische Universität München, 81675 Munich, Germany.Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

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Dirk H. Busch

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.Focus Group “Clinical Cell Processing and Purification,” Institute for Advanced Study, Technische Universität München, 81675 Munich, Germany.Clinical Cooperation Groups “Antigen-specific Immunotherapy” and “Immune Monitoring,” Helmholtz Center Munich (85764 Neuherberg) and Technische Universität München, 81675 Munich, Germany.DZIF–National Centre for Infection Research, 81675 Munich, Germany.

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For correspondence: dirk.busch@mikrobio.med.tum.de

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TCR-Ligand k_off Rate Correlates with the Protective Capacity of Antigen-Specific CD8⁺ T Cells for Adoptive Transfer

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