Sequence comparisons of different Epstein-Barr virus (EBV) isolates from different regions of the world have revealed unexpected virus strain heterogeneity. To what extent the sequence differences affect antiviral immunity is still unclear. For the representative EBV strains B95.8, M81, and AG876, the present study investigated the influence of sequence differences in known antigenic structures on the recognition by the cellular, adaptive immune system.
At protein level, the latency proteins of B95.8 and AG876 differed from M81 in 3.7% and 17.5%, respectively. In contrast, proteins of the lytic phase differed be-tween the viruses in only about 0.5%. A comparison of all known T-cell epitopes revealed that the three virus strains differ in half of all CD4+ and in one third of all CD8+ T-cell epitopes. When the epitope-flanking regions were included in these analyses, polymorphisms were found in nearly two thirds of all CD4+ and in over 40% of all CD8 + T-cell epitopes.
In functional studies, these amino acid exchanges had unpredictable effects on T-cell recognition, ranging from recognition enhancing to a complete loss of T-cell recognition. Amino acid exchanges in the hitherto neglected flanking regions also showed an influence on antigen processing and presentation and thus on the strength of T-cell recognition. Experiments with lymphoblastoid cell line (LCL)-stimulated T-cell lines provided evidence that the viral antigenome encompasses a sufficient number of T-cell epitopes that can confer immunity against different virus strains.
These results highlight the importance of viral strain heterogeneity for antiviral immunity. In addition, the described variable T-cell recognition of epitope variants has implications for the monitoring of EBV-specific immune responses, vaccine development and immunotherapy of EBV-associated diseases.
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Sequence comparisons of different Epstein-Barr virus (EBV) isolates from different regions of the world have revealed unexpected virus strain heterogeneity. To what extent the sequence differences affect antiviral immunity is still unclear. For the representative EBV strains B95.8, M81, and AG876, the present study investigated the influence of sequence differences in known antigenic structures on the recognition by the cellular, adaptive immune system.
At protein level, the latency proteins o...
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