Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals
Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals
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DOI：
10.1073/pnas.1105624108
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发表时间：
2011-05-31
影响因子：
11.1
通讯作者：
Chen, Weisan
中科院分区：
文献类型：
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作者：
Wu, Chao;Zanker, Damien;Chen, Weisan
免疫显性T细胞应答对于病毒清除是重要的。然而，免疫显性T细胞肽+ HLA糖蛋白表位的鉴定受到HLA多态性程度和预测算法局限性的阻碍。一个简单的，系统的方法已被用于筛选免疫显性CD 8（+）T细胞特异性。该分析针对健康的HLA-A2（+）供体，以允许与对充分研究的流感基质蛋白1表位的反应进行比较。尽管在我们的研究中，流感基质蛋白1在所有个体样本中均被检测到，但对该表位的应答仅在8个样本中的3个中是免疫显性的，而对于其他5个样本，突出的CD 8（+）T细胞应答倾向于集中在来自流感核蛋白的各种肽上，这些肽不是由HLA-A2呈递的。重要的是，在这里确定的四个免疫显性T细胞表位中，只有一个会被当前的预测程序检测到。其他三种肽要么被认为太长，要么被归类为不含典型的HLA结合基序。我们的数据强调了系统分析对于发现来自病毒和肿瘤的HLA依赖性免疫显性CD 8（+）T细胞表位的重要性。当我们寻求开发依赖于T细胞介导的免疫的靶向免疫疗法和疫苗策略时，专注于HLA-A2和预测算法可能过于局限。
Immunodominant T-cell responses are important for virus clearance. However, the identification of immunodominant T-cell peptide + HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for immunodominant CD8(+) T-cell specificities. The analysis targeted healthy HLA-A2(+) donors to allow comparison with responses to the well-studied influenza matrix protein 1 epitope. Although influenza matrix protein 1 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three of eight, whereas for the other five, prominent CD8(+) T-cell responses tended to focus on various peptides from the influenza nucleoprotein that were not presented by HLA-A2. Importantly, with the four immunodominant T-cell epitopes identified here, only one would have been detected by the current prediction programs. The other three peptides would have been either considered too long or classified as not containing typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8(+) T-cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.