Epstein-Barr virus strain heterogeneity impairs human T-cell immunity
| Autor: | K. Witter, Nina Körber, Michael Dieckmeyer, Dinesh Adhikary, Andreas Moosmann, Simon Stützle, Ana Cirac, Uta Behrends, Josef Mautner, Henri Jacques Delecluse, Tanja Bauer |
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| Jazyk: | němčina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Epstein-Barr Virus Infections Herpesvirus 4 Human Low protein Immunology Population T-cell Therapy Epstein-barr Virus Strain Variation Epitope Immunity Epitopes T-Lymphocyte Biology CD8-Positive T-Lymphocytes medicine.disease_cause Virus 03 medical and health sciences Immune system Antigen medicine Immunology and Allergy Humans education Antigens Viral education.field_of_study Genetic Variation Virology Epstein–Barr virus 030104 developmental biology Oncology |
| Zdroj: | Cancer Immunol. Immunother. 67, 663-674 (2018) |
| Popis: | The Epstein-Barr virus (EBV) establishes lifelong infections in > 90% of the human population. Although contained as asymptomatic infection by the immune system in most individuals, EBV is associated with the pathogenesis of approximately 1.5% of all cancers in humans. Some of these EBV-associated tumors have been successfully treated by the infusion of virus-specific T-cell lines. Recent sequence analyses of a large number of viral isolates suggested that distinct EBV strains have evolved in different parts of the world. Here, we assessed the impact of such sequence variations on EBV-specific T-cell immunity. With the exceptions of EBNA2 and the EBNA3 family of proteins, an overall low protein sequence disparity of about 1% was noted between Asian viral isolates, including the newly characterized M81 strain, and the prototypic EBV type 1 and type 2 strains. However, when T-cell epitopes including their flanking regions were compared, a substantial proportion was found to be polymorphic in different EBV strains. Importantly, CD4+ and CD8+ T-cell clones specific for viral epitopes from one strain often showed diminished recognition of the corresponding epitopes in other strains. In addition, T-cell recognition of a conserved epitope was affected by amino acid exchanges within the epitope flanking region. Moreover, the CD8+ T-cell response against polymorphic epitopes varied between donors and often ignored antigen variants. These results demonstrate that viral strain heterogeneity may impair antiviral T-cell immunity and suggest that immunotherapeutic approaches against EBV should preferably target broad sets of conserved epitopes including their flanking regions. |
| Databáze: | OpenAIRE |
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