Identification of an HLA A*0201-restricted CD8(+) T-cell epitope for the glycoprotein B homolog of human herpesvirus 8.
Identification of an HLA A*0201-restricted CD8(+) T-cell epitope for the glycoprotein B homolog of human herpesvirus 8.
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DOI：
10.1182/blood.v99.9.3360
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发表时间：
2002-05
期刊：
影响因子：
20.3
通讯作者：
Qiong J. Wang;Xiao-li Huang;G. Rappocciolo;F. Jenkins;W. Hildebrand;Zheng Fan;E. Thomas;C. Rinaldo
中科院分区：
文献类型：
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作者：
Qiong J. Wang;Xiao-li Huang;G. Rappocciolo;F. Jenkins;W. Hildebrand;Zheng Fan;E. Thomas;C. Rinaldo
人疱疹病毒8型（HHV-8;卡波西肉瘤相关疱疹病毒）特异性细胞毒性T淋巴细胞（CTL）和干扰素-γ（IFN-γ）对HHV-8复制裂解周期中产生的蛋白质的应答由HLA I类限制性CD 8（+）T细胞介导。我们基于HLA A*0201结合基序的预测模型，表征了CD 8（+）T细胞对来自5种HHV-8裂解周期蛋白的25种肽的反应的精细特异性。来源于EB病毒糖蛋白B（gB）同源物的25种HLA A*0201肽之一（gB（492-500）; LMWYELSKI;单字母氨基酸编码）与HLA A*0201结合，并刺激来自HHV-8（+）、HLA A*0201人群的CD 8（+）T细胞中的IFN-γ应答，但不刺激HHV-8血清阴性或非HLA A*0201人群。该肽还诱导IFN-γ和CTL对天然加工的gB蛋白的反应性。该肽是HHV-8的主要免疫原性表位，如通过当gB（492-500）被自体树突细胞呈递时，在来自5名HHV-8血清阳性、HLA A*0201的人中的5名的外周血单核细胞中诱导IFN-γ应答所指示的。T细胞对gB（492-500）的反应性与血液中可检测到的HHV-8 DNA无关。这些数据表明，CD 8（+）T细胞识别HHV-8裂解周期蛋白gB的HLA A*0201限制性表位，特别是当由树突状细胞呈递时。该表位在CD 8（+）T细胞控制HHV-8感染中可能是重要的。
Human herpesvirus 8 (HHV-8; Kaposi sarcoma-associated herpesvirus)-specific cytotoxic T-lymphocyte (CTL) and interferon-gamma (IFN-gamma) responses to proteins produced during the lytic cycle of HHV-8 replication are mediated by HLA class I-restricted, CD8(+) T cells. We have characterized the fine specificity of the CD8(+) T-cell response to 25 peptides derived from 5 HHV-8 lytic cycle proteins based on a prediction model for HLA A*0201 binding motifs. One of the 25 HLA A*0201 peptides derived from the glycoprotein B (gB) homolog of Epstein-Barr virus (gB(492-500); LMWYELSKI; single-letter amino acid codes) bound to HLA A*0201 and stimulated IFN-gamma responses in CD8(+) T cells from HHV-8(+), HLA A*0201 persons, but not HHV-8-seronegative or non-HLA A*0201 persons. The peptide also induced IFN-gamma and CTL reactivity to naturally processed gB protein. The peptide was a major immunogenic epitope of HHV-8 as indicated by induction of IFN-gamma responses in peripheral blood mononuclear cells from 5 of 5 HHV-8 seropositive, HLA A*0201 persons when gB(492-500) was presented by autologous dendritic cells. T-cell reactivity to gB(492-500) was not related to detectable HHV-8 DNA in the blood. These data show that CD8(+) T cells recognize an HLA A*0201-restricted epitope for HHV-8 lytic cycle protein gB, particularly when presented by dendritic cells. This epitope may be important in control of HHV-8 infection by CD8(+) T cells.