Brander C, O'Connor P, Suscovich T, Jones N G, Lee Y, Kedes D, Ganem D, Martin J, Osmond D, Southwood S, Sette A, Walker B D, Scadden D T
AIDS Research Center and Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
J Infect Dis. 2001 Jul 15;184(2):119-26. doi: 10.1086/322003. Epub 2001 Jun 18.
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-A0201 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-A0201-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.
细胞毒性T淋巴细胞(CTL)识别并杀死病毒感染的细胞,有助于对病毒复制进行免疫控制。对于许多疱疹病毒(如EB病毒和巨细胞病毒),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,且特征仍不明确。我们使用基于人类白细胞抗原(HLA)结合基序的表位预测算法,从8个KSHV开放阅读框(ORF)中鉴定出37个HLA-A0201结合肽。在对KSHV感染者的外周血单个核细胞进行体外刺激后,在2名HLA-A0201阳性受试者中检测到针对KSHV卡波辛蛋白(ORF K12)中1个肽的CTL反应。通过HLA限制性分析和肽滴定试验确定了最佳CTL表位。这些数据描述了一个被CTL靶向的潜伏期病毒基因产物,这可能与KSHV免疫发病机制相关。