Bibliographic Details
| Title: |
Hepatitis E Virus (HEV)-Specific T Cell Receptor Cross-Recognition: Implications for Immunotherapy |
| Authors: |
Chai Fen Soon, Shihong Zhang, Pothakamuri Venkata Suneetha, Dinler Amaral Antunes, Michael Peter Manns, Solaiman Raha, Christian Schultze-Florey, Immo Prinz, Heiner Wedemeyer, Margaret Sällberg Chen, Markus Cornberg |
| Source: |
Frontiers in Immunology, Vol 10 (2019) |
| Publisher Information: |
Frontiers Media S.A., 2019. |
| Publication Year: |
2019 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
CD8+ T cells, cross-reactivity, T cell therapy, immunotherapy, T cell receptor (TCR), TCR redirection, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02076/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2019.02076 |
| Access URL: |
https://doaj.org/article/400fb658755a4169a0845c8b630f7822 |
| Accession Number: |
edsdoj.400fb658755a4169a0845c8b630f7822 |
| Database: |
Directory of Open Access Journals |
