Hepatitis E Virus (HEV)-Specific T Cell Receptor Cross-Recognition: Implications for Immunotherapy

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dc.citation.firstpage2076en_US
dc.citation.journalTitleFrontiers in Immunologyen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorSoon, Chai Fenen_US
dc.contributor.authorZhang, Shihongen_US
dc.contributor.authorSuneetha, Pothakamuri Venkataen_US
dc.contributor.authorAntunes, Dinler Amaralen_US
dc.contributor.authorManns, Michael Peteren_US
dc.contributor.authorRaha, Solaimanen_US
dc.contributor.authorSchultze-Florey, Christianen_US
dc.contributor.authorPrinz, Immoen_US
dc.contributor.authorWedemeyer, Heineren_US
dc.contributor.authorSällberg Chen, Margareten_US
dc.contributor.authorCornberg, Markusen_US
dc.date.accessioned2021-10-06T14:15:47Zen_US
dc.date.available2021-10-06T14:15:47Zen_US
dc.date.issued2019en_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.identifier.citationSoon, Chai Fen, Zhang, Shihong, Suneetha, Pothakamuri Venkata, et al.. "Hepatitis E Virus (HEV)-Specific T Cell Receptor Cross-Recognition: Implications for Immunotherapy." <i>Frontiers in Immunology,</i> 10, (2019) Frontiers: 2076. https://doi.org/10.3389/fimmu.2019.02076.en_US
dc.identifier.digitalfimmu-10-02076en_US
dc.identifier.doihttps://doi.org/10.3389/fimmu.2019.02076en_US
dc.identifier.urihttps://hdl.handle.net/1911/111483en_US
dc.language.isoengen_US
dc.publisherFrontiersen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleHepatitis E Virus (HEV)-Specific T Cell Receptor Cross-Recognition: Implications for Immunotherapyen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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