Micheletti Fabiola, Monini Paolo, Fortini Cinzia, Rimessi Paola, Bazzaro Martina, Andreoni Massimo, Giuliani Massimo, Traniello Serena, Ensoli Barbara, Gavioli Riccardo
Department of Biochemistry and Molecular Biology, University of Ferrara, Italy.
Immunology. 2002 Jul;106(3):395-403. doi: 10.1046/j.1365-2567.2002.01424.x.
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.
人类疱疹病毒8型（HHV-8）是一种人类γ2疱疹病毒，与卡波西肉瘤（KS）、原发性渗出性淋巴瘤和卡斯尔曼病的发生有关。由于细胞毒性T淋巴细胞（CTL）反应在控制疱疹病毒感染中起关键作用，因此识别和表征HHV-8病毒抗原的CTL靶表位很重要。在本研究中，我们利用肽结合基序，从分别为HHV-8潜伏性抗原和裂解性抗原的卡波西蛋白A和糖蛋白H（gH）中筛选出潜在的人类白细胞抗原（HLA）-A2结合肽。对HLA-A2结合肽在HHV-8阴性健康供体中诱导CTL反应的能力进行了检测。通过这种方法，我们发现大多数个体对两个源自HHV-8的CTL表位产生反应，即源自卡波西蛋白A的VLLNGWRWRL（氨基酸16-25）和源自gH的FLNWQNLLNV（氨基酸59-68）。此外，在感染HHV-8的无病个体中检测到对这些表位的记忆CTL反应，这表明这两个表位是体内CTL介导免疫的相关靶标。所鉴定的表位可用于研究针对HHV-8相关恶性肿瘤的免疫治疗策略。
