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.

Identification of cytotoxic T lymphocyte epitopes of human herpesvirus 8

MICHELETTI, Fabiola
Primo
;
FORTINI, Cinzia;RIMESSI, Paola;TRANIELLO, Maria Serena;GAVIOLI, Riccardo
Ultimo
2002

Abstract

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.
2002
Micheletti, Fabiola; Monini, P.; Fortini, Cinzia; Rimessi, Paola; Bazzaro, M.; Andreoni, M.; Giuliani, M.; Traniello, Maria Serena; Ensoli, B.; Gavioli, Riccardo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1210161
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