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

Schreiber, Sophia; Honz, Melanie; Mamozai, Weeda; Kurktschiev, Peter; Schiemann, Matthias; Witter, Klaus; Moore, Eugene; Zielinski, Christina; Sette, Alessandro; Protzer, Ulrike; Wisskirchen, Karin

doi:10.1016/j.omtm.2021.10.012

Benutzer: Gast

2021

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Dokumenttyp:: Journal Article
Autor(en):: Schreiber, Sophia; Honz, Melanie; Mamozai, Weeda; Kurktschiev, Peter; Schiemann, Matthias; Witter, Klaus; Moore, Eugene; Zielinski, Christina; Sette, Alessandro; Protzer, Ulrike; Wisskirchen, Karin
Titel:: Characterization of a library of 20 HBV-specific MHC class II-restricted T cell receptors.
Abstract:: 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.
Zeitschriftentitel:: Mol Ther Methods Clin Dev
Jahr:: 2021
Band / Volume:: 23
Seitenangaben Beitrag:: 476-489
Volltext / DOI:: doi:10.1016/j.omtm.2021.10.012
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/34853796
Print-ISSN:: 2329-0501
TUM Einrichtung:: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene; Institut für Virologie
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