Identification of CD8+ T cell epitopes within lytic antigens of human herpes virus 8.
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.
Ribechini
Eliana
E
Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
Fortini
Cinzia
C
Marastoni
Mauro
M
Traniello
Serena
S
Spisani
Susanna
S
Monini
Paolo
P
Gavioli
Riccardo
R
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D005814:Genes, Viral; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D059871:HLA-A24 Antigen; D015793:HLA-B7 Antigen / Q000378:metabolism; D006566:Herpesviridae Infections / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D016366:Open Reading Frames; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D015793:HLA-B7 Antigen