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The Journal of Immunology, 2006, 176: 923-930.
Copyright © 2006 by The American Association of Immunologists

Identification of CD8+ T Cell Epitopes within Lytic Antigens of Human Herpes Virus 81

Eliana Ribechini*, Cinzia Fortini*, Mauro Marastoni{dagger}, Serena Traniello*, Susanna Spisani*, Paolo Monini{ddagger} and Riccardo Gavioli2,*

* Department of Biochemistry and Molecular Biology and {dagger} Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy; and {ddagger} Laboratory of Virology, Istituto Superiore di Sanità, Roma, Italy

The human herpesvirus 8 (HHV-8) is a {gamma} herpesvirus with oncogenic potential which establishes a chronic infection that is normally controlled by the immune system of healthy individuals. In particular, CTL responses seem to play a key role in control of the infection. In this study, we characterized epitope-specific CTL responses in healthy HHV-8-seropositive individuals against four HHV-8 lytic Ags: open reading frames (ORF) 26, 70, K3, and K5. We found that the majority of subjects responded to at least one HHV-8 lytic Ag-derived epitope, and some of these epitopes represented dominant targets, suggesting that they could be relevant targets of CTL-mediated immunity in vivo, and may be involved in host control of HHV-8. Specifically, we identified three CTL epitopes from ORF 26, which are presented by HLA-A2, six CTL epitopes from ORF 70 presented by HLA-A2 (three epitopes), -A24 (two epitopes), and -B7 (one epitope), three CTL epitopes from ORF K3 presented by HLA-A2 (two epitopes) and -B7 (one epitope), and one HLA-A2 presented epitope derived from ORF K5. The identified epitopes may be regarded as useful tools for understanding the role of CTL responses to lytic Ags in individuals affected by HHV-8-associated disorders, and for the development of immunotherapies for the treatment/prevention of HHV-8-associated malignancies.




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