Hepatitis E Virus (HEV)-Specific T Cell Receptor Cross-Recognition: Implications for Immunotherapy.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Soon, Chai FenZhang, Shihong
Suneetha, Pothakamuri Venkata
Antunes, Dinler Amaral
Manns, Michael Peter
Raha, Solaiman
Schultze-Florey, Christian
Prinz, Immo
Wedemeyer, Heiner
Sällberg Chen, Margaret
Cornberg, Markus
Issue Date
2019-01-01
Metadata
Show full item recordAbstract
T 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.Citation
Front Immunol. 2019 Sep 4;10:2076. doi: 10.3389/fimmu.2019.02076. eCollection 2019.Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.Publisher
FrontiersJournal
Frontiers in ImmunologyPubMed ID
31552033Type
ArticleLanguage
enISSN
1664-3224ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2019.02076
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
Related articles
- Defining virus-specific CD8+ TCR repertoires for therapeutic regeneration of T cells against chronic hepatitis E.
- Authors: Soon CF, Behrendt P, Todt D, Manns MP, Wedemeyer H, Sällberg Chen M, Cornberg M
- Issue date: 2019 Oct
- Chronic TCR-MHC (self)-interactions limit the functional potential of TCR affinity-increased CD8 T lymphocytes.
- Authors: Duong MN, Erdes E, Hebeisen M, Rufer N
- Issue date: 2019 Nov 5
- Development of a T cell receptor targeting an HLA-A*0201 restricted epitope from the cancer-testis antigen SSX2 for adoptive immunotherapy of cancer.
- Authors: Abate-Daga D, Speiser DE, Chinnasamy N, Zheng Z, Xu H, Feldman SA, Rosenberg SA, Morgan RA
- Issue date: 2014
- Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor histocompatibility antigen HA-2-specific T-cell receptor complexes expressing a conserved alpha joining region.
- Authors: Heemskerk MH, Hoogeboom M, de Paus RA, Kester MG, van der Hoorn MA, Goulmy E, Willemze R, Falkenburg JH
- Issue date: 2003 Nov 15
- Structural Basis for Clonal Diversity of the Public T Cell Response to a Dominant Human Cytomegalovirus Epitope.
- Authors: Yang X, Gao M, Chen G, Pierce BG, Lu J, Weng NP, Mariuzza RA
- Issue date: 2015 Nov 27