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Epstein-Barr virus strain heterogeneity impairs human T-cell immunity.
Cancer Immunol. Immunother. 67, 663-674 (2018)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
T-cell Therapy ; Epstein-barr Virus ; Strain Variation ; Epitope ; Immunity; Antigen Presentation; Lymphoproliferative Disorders; Clinical-trial; Helper-cells; Recognition; Disease; Diversity; Infection; Therapy; Transplant
ISSN (print) / ISBN
0340-7004
e-ISSN
1432-0851
Journal
Cancer Immunology, Immunotherapy
Quellenangaben
Volume: 67,
Issue: 4,
Pages: 663-674
Publisher
Springer
Publishing Place
New York
Non-patent literature
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Reviewing status
Peer reviewed