Immune Reactivity Against a Novel HLA-A3-Restricted Influenza Virus Peptide Identified by Predictive Algorithms and Interferon- Quantitative PCR
Immune Reactivity Against a Novel HLA-A3-Restricted Influenza Virus Peptide Identified by Predictive Algorithms and Interferon- Quantitative PCR
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DOI：
10.1097/00002371-200301000-00005
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发表时间：
2003-01
影响因子：
3.9
通讯作者：
A. Trojan;M. Urosevic;J. Hummerjohann;R. Giger;U. Schanz;R. Stahel
中科院分区：
文献类型：
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作者：
A. Trojan;M. Urosevic;J. Hummerjohann;R. Giger;U. Schanz;R. Stahel
使用最常见的人类主要组织相容性复合体（MHC）等位基因的适当抗原肽是扩增自体细胞毒性隔室和细胞毒性T细胞介导的免疫的发展所必需的。人类MHC的A2等位基因在识别针对肿瘤和病毒表位的肽特异性细胞毒性T细胞（CTL）中起重要作用。基于计算机的预测算法，这是在互联网上，已经证明是适用于新的CTL表位的鉴定。使用生物信息学方法，作者已经鉴定了新的流感基质蛋白衍生的和HLA-A3限制的9-mer肽RLEDVFAGK，其能够诱导肽特异性CTL反应性。来自健康个体和肺癌患者的外周血单核细胞（PBMC）用该肽和充分表征的HLA-A2限制性甲型流感病毒基质肽58 -66 GILGFVFTL脉冲。使用定量PCR（TaqMan; Applied Biosystems，Foster City，CA，U.S.A），通过测量在体外刺激时1型细胞因子（IFN-）表达的变化来确定两种肽的反应性。肽特异性反应性与随后确定的测试个体的MHC I类等位基因匹配良好。本研究的结果表明，使用生物信息学和基于PCR的筛选系统的T细胞反应性的监测可能允许识别新的CTL表位。
The use of appropriate antigenic peptides for the most common human major histocompatibility complex (MHC) alleles is required for the amplification of the autologous cytotoxic compartment and the development of cytotoxic T cell-mediated immunity. The human A2 allele of the MHC plays an important role for the identification of peptide-specific cytotoxic T cells (CTL) against tumor and viral epitopes. Computer-based prediction algorithms, which are available on the Internet, have already proved to be applicable for the identification of novel CTL epitopes. Using the bioinformatics approach, the authors have identified the novel influenza matrix protein-derived and HLA-A3-restricted 9-mer peptide RLEDVFAGK capable of inducing peptide specific CTL reactivity. Peripheral blood mononuclear cells (PBMC) from healthy individuals and patients with lung cancer were pulsed with this peptide and with the well-characterized HLA-A2-restricted influenza A virus matrix peptide58–66 GILGFVFTL. Using quantitative PCR (TaqMan; Applied Biosystems, Foster City, CA, U.S.A), reactivity for both peptides was determined by measuring the change in type 1 cytokine (IFN-) expression upon in vitro stimulation. Peptide-specific reactivity matched well with the subsequently determined MHC-class I alleles of the tested individuals. Results from this study indicate that the use of bioinformatics and the PCR-based screening system for the monitoring of T cell reactivity may allow for the identification of novel CTL epitopes.