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Schreiber, S. ; Honz, M.* ; Mamozai, W.* ; Kurktschiev, P.* ; Schiemann, M.* ; Witter, K.* ; Moore, E.* ; Zielinski, C.* ; Sette, A.* ; Protzer, U. ; Wisskirchen, K.

Characterization of a library of 20 HBV-specific MHC class II-restricted T cell receptors.

Mol.Ther.-Methods Clin. Dev. 23, 476-489 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
CD4+ T cells play an important role in the immune response against cancer and infectious diseases. However, mechanistic details of their helper function in hepatitis B virus (HBV) infection in particular, or their advantage for adoptive T cell therapy remain poorly understood as experimental and therapeutic tools are missing. Therefore, we identified, cloned, and characterized a comprehensive library of 20 MHC class II-restricted HBV-specific T cell receptors (TCRs) from donors with acute or resolved HBV infection. The TCRs were restricted by nine different MHC II molecules and specific for eight different epitopes derived from intracellularly processed HBV envelope, core, and polymerase proteins. Retroviral transduction resulted in a robust expression of all TCRs on primary T cells. A high functional avidity was measured for all TCRs specific for epitopes S17, S21, S36, and P774 (half-maximal effective concentration [EC50] <10 nM), or C61 and preS9 (EC50 <100 nM). Eight TCRs recognized peptide variants of HBV genotypes A to D. Both CD4+ and CD8+ T cells transduced with the MHC II-restricted TCRs were polyfunctional, producing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and granzyme B (GrzB), and killed peptide-loaded target cells. Our set of MHC class II-restricted TCRs represents an important tool for elucidating CD4+ T cell help in viral infection with potential benefit for T cell therapy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Adoptive T Cell Therapy ; Cd4 T Cells + ; Chronic Hepatitis B ; Hbv Clearance ; Hepatitis B Virus Infection ; Hepatocellular Carcinoma ; Mhc Class Ii-restricted T Cell Receptors ; Retroviral Transduction ; T Cell Help ; Tcr Expression; Hepatitis-b-virus; Chimeric Antigen Receptor; Viral-infections; Gene Polymorphisms; Cytotoxic Activity; Surface-antigen; Cd4; Association; Immunity; Expression
ISSN (print) / ISBN 2329-0501
e-ISSN 2329-0501
Zeitschrift Molecular Therapy. Methods & Clinical Development
Quellenangaben Band: 23, Heft: , Seiten: 476-489 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen NIH NIAID (United States)
DFG through the TUM International Graduate School of Science and Engineering (IGSSE)
German Center for Infection Research (DZIF)
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)