Identification of cytotoxic T lymphocyte epitopes of human herpesvirus 8.
The human herpesvirus 8 (HHV-8) is a human gamma2-herpesvirus that is implicated in the development of Kaposi's sarcoma (KS), primary effusion lymphoma and Castelman's disease. Since the responses of cytotoxic T lymphocytes (CTL) play a key role in the control of herpesvirus infection, it is important to identify and to characterize the CTL target epitopes of HHV-8 viral antigens. In this study, using peptide-binding motifs, we selected potential human leucocyte antigen (HLA)-A2-binding peptides from kaposin A and glycoprotein H (gH), that are latent and lytic HHV-8 antigens, respectively. HLA-A2-binding peptides were tested for their capacity to induce CTL responses in HHV-8-negative healthy donors. By this approach, we found that the majority of individuals responded to two HHV-8-derived CTL epitopes, namely, VLLNGWRWRL (amino acids 16-25), which derives from kaposin A, and FLNWQNLLNV (amino acids 59-68), which derives from gH. In addition, memory CTL responses to these epitopes were detected in disease-free individuals infected by HHV-8 demonstrating that the two epitopes are relevant targets of CTL-mediated immunity in vivo. The identified epitopes may be investigated for the development of immunotherapeutic strategies against HHV-8-associated malignancies.
Micheletti
Fabiola
F
Department of Biochemistry and Molecular Biology, University of Ferrara, Italy.
Monini
Paolo
P
Fortini
Cinzia
C
Rimessi
Paola
P
Bazzaro
Martina
M
Andreoni
Massimo
M
Giuliani
Massimo
M
Traniello
Serena
S
Ensoli
Barbara
B
Gavioli
Riccardo
R
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000737:chemistry; D015789:HLA-A2 Antigen / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C464461:glycoprotein H, human herpesvirus 8; C120136:kaposin B protein, Human herpesvirus 8