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dc.contributor.authorSoon, Chai Fen
dc.contributor.authorZhang, Shihong
dc.contributor.authorSuneetha, Pothakamuri Venkata
dc.contributor.authorAntunes, Dinler Amaral
dc.contributor.authorManns, Michael Peter
dc.contributor.authorRaha, Solaiman
dc.contributor.authorSchultze-Florey, Christian
dc.contributor.authorPrinz, Immo
dc.contributor.authorWedemeyer, Heiner
dc.contributor.authorSällberg Chen, Margaret
dc.contributor.authorCornberg, Markus
dc.identifier.citationFront Immunol. 2019 Sep 4;10:2076. doi: 10.3389/fimmu.2019.02076. eCollection 2019.en_US
dc.description.abstractT cell immunotherapy is a concept developed for the treatment of cancer and infectious diseases, based on cytotoxic T lymphocytes to target tumor- or pathogen-specific antigens. Antigen-specificity of the T cell receptors (TCRs) is an important selection criterion in the developmental design of immunotherapy. However, off-target specificity is a possible autoimmunity concern if the engineered antigen-specific T cells are cross-reacting to self-peptides in-vivo. In our recent work, we identified several hepatitis E virus (HEV)-specific TCRs as potential candidates to be developed into T cell therapy to treat chronic hepatitis E. One of the identified TCRs, targeting a HLA-A2-restricted epitope at the RNA-dependent RNA polymerase (HEV-1527: LLWNTVWNM), possessed a unique multiple glycine motif in the TCR-β CDR3, which might be a factor inducing cross-reactivity. The aim of our study was to explore if this TCR could cross-recognize self-peptides to underlay autoimmunity. Indeed, we found that this HEV-1527-specific TCR could also cross-recognize an apoptosis-related epitope, Nonmuscle Myosin Heavy Chain 9 (MYH9-478: QLFNHTMFI). While this TCR had dual specificities to both viral epitope and a self-antigen by double Dextramer binding, it was selectively functional against HEV-1527 but not activated against MYH9-478. The consecutive glycine motif in β chain may be the reason promoting TCR binding promiscuity to recognize a secondary target, thereby facilitating cross-recognition. In conclusion, candidate TCRs for immunotherapy development should be screened for autoimmune potential, especially when the TCRs exhibit unique sequence pattern.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.subjectCD8+ T cellsen_US
dc.subjectT cell receptor (TCR)en_US
dc.subjectT cell therapyen_US
dc.subjectTCR redirectionen_US
dc.subjecthepatitis E virus (HEV)en_US
dc.titleHepatitis E Virus (HEV)-Specific T Cell Receptor Cross-Recognition: Implications for Immunotherapy.en_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in Immunologyen_US
dc.source.journaltitleFrontiers in immunology

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