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Epstein-Barr virus strain heterogeneity impairs human T-cell immunity.
- Source :
- Cancer Immunology, Immunotherapy; Apr2018, Vol. 67 Issue 4, p663-674, 12p
- Publication Year :
- 2018
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- EPSTEIN-Barr virus
T cells
CD4 antigen
IMMUNE system
TUMOR treatment
Subjects
Details
- Language :
- English
- ISSN :
- 03407004
- Volume :
- 67
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Cancer Immunology, Immunotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 128598220
- Full Text :
- https://doi.org/10.1007/s00262-018-2118-z