An integrative approach to CTL epitope prediction: A combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions
An integrative approach to CTL epitope prediction: A combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions
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DOI：
10.1002/eji.200425811
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发表时间：
2005-08-01
影响因子：
5.4
通讯作者：
Nielsen, M
中科院分区：
文献类型：
--
作者：
Larsen, MV;Lundegaard, C;Nielsen, M
反向免疫遗传学方法试图优化候选表位的选择，从而最大限度地减少鉴定新表位所需的实验努力。在预测细胞毒性T细胞表位时，主要关注的是高度特异性的MHC I类结合事件。在MHC I类结合之前，还开发了预测抗原加工步骤的方法，包括蛋白酶体切割和与抗原加工相关的转运蛋白（TAP）运输效率。在这里，我们使用从SYFPEITHI数据库获得的数据集来表明，综合MHC I类结合亲和力，TAP运输效率和c端蛋白酶体切割的预测方法优于任何单独的方法。利用来自洛斯阿拉莫斯数据库的独立HIV表位评估数据集，验证了综合方法的有效性。综合方法的性能明显高于现有的两种预测方法BIMAS和SYFPEITHI。为了鉴定HIV数据集中85%的表位，在使用BIMAS和SYFPEITHI方法选择候选表位时，必须分别检测HIV蛋白中所有可能的非命名物的9%和10%。当使用综合方法时，这个数字减少到7%。在实践中，这意味着当使用集成方法时，以85%的概率识别假设蛋白质中的表位所需的实验努力减少了20-30%。该方法可在http://www.cbs.dtu.dk/services/NetCTL上获得。补充材料可在http://www.cbs.dtu.dk/suppl/immunology/CTL.php上获得。
Reverse immunogenetic approaches attempt to optimize the selection of candidate epitopes, and thus minimize the experimental effort needed to identify new epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on the highly specific MHC class I binding event. Methods have also been developed for predicting the antigen-processing steps preceding MHC class I binding, including proteasomal cleavage and transporter associated with antigen processing (TAP) transport efficiency. Here, we use a dataset obtained from the SYFPEITHI database to show that a method integrating predictions of MHC class I binding affinity, TAP transport efficiency, and C-terminal proteasomal cleavage outperforms any of the individual methods. Using an independent evaluation dataset of HIV epitopes from the Los Alamos database, the validity of the integrated method is confirmed. The performance of the integrated method is found to be significantly higher than that of the two publicly available prediction methods BIMAS and SYFPEITHI. To identify 85% of the epitopes in the HIV dataset, 9% and 10% of all possible nonamers in the HIV proteins must be tested when using the BIMAS and SYFPEITHI methods, respectively, for the selection of candidate epitopes. This number is reduced to 7% when using the integrated method. In practical terms, this means that the experimental effort needed to identify an epitope in a hypothetical protein with 85% probability is reduced by 20-30% when using the integrated method.The method is available at http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/CTL.php.