Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus.
Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus.
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DOI：
10.1099/vir.0.82391-0
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发表时间：
2007-04
期刊：
影响因子：
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通讯作者：
T. Tagmyer;J. Craigo;S. Cook;C. Issel;R. Montelaro
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作者：
T. Tagmyer;J. Craigo;S. Cook;C. Issel;R. Montelaro
马传染性贫血病毒（EIAV）感染为研究慢病毒感染和疾病的自然免疫控制以及保护性和增强疫苗免疫的机制提供了有价值的模型。我们之前假设EIAV包膜（Env）蛋白gp90和gp45是疫苗效力的主要决定因素，并且减毒病毒疫苗的保护性免疫发展可能与免疫反应从免疫显性、可变Env片段向免疫隐性、保守的Env序列的逐渐重定向有关。虽然已经确定了Env的抗体中和决定因素，但迄今为止还没有对EIAV Env蛋白的淋巴增生性（T-helper, Th）和细胞毒性t细胞（CTL）表位进行全面分析。因此，在当前的研究中，我们使用合成肽方法确定了与保护性疫苗免疫相关的EIAV Env区域，其中12匹马接种了EIAV（D9）减毒疫苗，2匹无症状的马实验感染了表达与疫苗株相同Env蛋白的EIAV（PV）毒株。这些研究的结果确定了EIAV的Env蛋白中与保护性免疫相关的17个广泛反应性Th肽和6个广泛反应性CTL肽。因此，这些数据首次提供了EIAV env特异性细胞区域的全面图谱，可用于检查保护性免疫的发展并评估保护性免疫的潜在细胞免疫决定因素。
Equine infectious anemia virus (EIAV) infection of horses provides a valuable model for examining the natural immunological control of lentivirus infection and disease and the mechanisms of protective and enhancing vaccine immunity. We have previously hypothesized that the EIAV envelope (Env) proteins gp90 and gp45 are major determinants of vaccine efficacy, and that the development of protective immunity by attenuated viral vaccines may be associated with the progressive redirection of immune responses from immunodominant, variable Env segments to immunorecessive, conserved Env sequences. Whilst the antibody-neutralization determinants of Env have been defined, there are to date no comprehensive analyses of the lymphoproliferative (T-helper, Th) and cytotoxic T-cell (CTL) epitopes of the EIAV Env proteins. Thus, in the current study, synthetic-peptide methodologies were used to define regions of EIAV Env associated with protective vaccine immunity in a panel of 12 horses inoculated with the attenuated EIAV(D9) vaccine and two asymptomatic carrier horses infected experimentally with the virulent EIAV(PV) strain expressing the same Env protein as the vaccine strain. The results of these studies identified 17 broadly reactive Th peptides and six broadly reactive CTL peptides in the Env proteins of EIAV that were associated with protective immunity. Thus, these data provide for the first time a comprehensive mapping of EIAV Env-specific cellular regions that can be used to examine the development of protective immunity and to evaluate potential cellular immune determinants of protective immunity.