Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi's sarcoma-associated herpesvirus kaposin protein
Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi's sarcoma-associated herpesvirus kaposin protein
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DOI：
10.1086/322003
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发表时间：
2001-07-15
影响因子：
6.4
通讯作者：
Scadden, DT
中科院分区：
文献类型：
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作者：
Brander, C;O'Connor, P;Scadden, DT
细胞毒性 T 淋巴细胞 (CTL) 识别并杀死病毒感染的细胞，有助于病毒复制的免疫控制。对于许多疱疹病毒（例如 Epstein-Barr 和巨细胞病毒），在感染者中可以很容易地检测到病毒特异性 CTL 反应，但针对卡波西肉瘤相关疱疹病毒 (KSHV) 的 CTL 反应似乎较弱，且特征仍不清楚。使用基于人类白细胞抗原 (HLA) 结合基序的表位预测算法，我们从 8 个 KSHV 开放阅读框 (ORF) 中鉴定出 37 个 HLA-A*0201 结合肽。对 KSHV 感染者的外周血单核细胞进行体外刺激后，在 2 名 HLA-A*0201 阳性受试者中检测到针对 KSHV 卡波蛋白 (ORF K12) 中的 1 个肽的 CTL 反应。通过 HLA 限制性分析和肽滴定测定确定了最佳 CTL 表位。这些数据描述了 CTL 靶向的潜伏期病毒基因产物，可能与 KSHV 免疫发病机制相关。
Cytotoxic T lymphocytes (CTL) recognize and kill virus-infected cells and contribute to immunologic control of viral replication. For many herpesviruses (e.g., Epstein-Barr and cytomegalovirus), virus-specific CTL responses can be readily detected in infected persons, but CTL responses against Kaposi's sarcoma-associated herpesvirus (KSHV) appear to be weak and remain poorly characterized. Using a human leukocyte antigen (HLA) binding motif-based epitope prediction algorithm, we identified 37 HLA-A*0201 binding peptides from 8 KSHV open-reading frames (ORFs). After in vitro stimulation of peripheral blood mononuclear cells from KSHV-infected persons, CTL responses against 1 peptide in the KSHV kaposin protein (ORF K12) were detected in 2 HLA-A*0201-positive subjects. The optimal CTL epitope was identified by HLA restriction analysis and peptide titration assays. These data describe a latent phase viral gene product targeted by CTL that may be relevant for KSHV immunopathogenesis.