School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.
BMC Bioinformatics. 2013 Feb 14;14:52. doi: 10.1186/1471-2105-14-52.
CD4+ T-cell epitopes play a crucial role in eliciting vigorous protective immune responses during peptide (epitope)-based vaccination. The prediction of these epitopes focuses on the peptide binding process by MHC class II proteins. The ability to account for MHC class II polymorphism is critical for epitope-based vaccine design tools, as different allelic variants can have different peptide repertoires. In addition, the specificity of CD4+ T-cells is often directed to a very limited set of immunodominant peptides in pathogen proteins. The ability to predict what epitopes are most likely to dominate an immune response remains a challenge.
We developed the computational tool Predivac to predict CD4+ T-cell epitopes. Predivac can make predictions for 95% of all MHC class II protein variants (allotypes), a substantial advance over other available methods. Predivac bases its prediction on the concept of specificity-determining residues. The performance of the method was assessed both for high-affinity HLA class II peptide binding and CD4+ T-cell epitope prediction. In terms of epitope prediction, Predivac outperformed three available pan-specific approaches (delivering the highest specificity). A central finding was the high accuracy delivered by the method in the identification of immunodominant and promiscuous CD4+ T-cell epitopes, which play an essential role in epitope-based vaccine design.
The comprehensive HLA class II allele coverage along with the high specificity in identifying immunodominant CD4+ T-cell epitopes makes Predivac a valuable tool to aid epitope-based vaccine design in the context of a genetically heterogeneous human population.The tool is available at: http://predivac.biosci.uq.edu.au/.
CD4+ T 细胞表位在基于肽（表位）的疫苗接种中激发强烈的保护性免疫反应中起着至关重要的作用。这些表位的预测主要集中在 MHC Ⅱ类蛋白的肽结合过程上。考虑 MHC Ⅱ类多态性的能力对于基于表位的疫苗设计工具至关重要，因为不同的等位变体可能具有不同的肽谱。此外，CD4+ T 细胞的特异性通常针对病原体蛋白中非常有限的一组免疫优势肽。预测哪些表位最有可能主导免疫反应仍然是一个挑战。
我们开发了计算工具 Predivac 来预测 CD4+ T 细胞表位。Predivac 可以对 95%的所有 MHC Ⅱ类蛋白变体（同种型）进行预测，这是对其他可用方法的重大改进。Predivac 基于特异性决定残基的概念进行预测。该方法的性能针对高亲和力 HLA Ⅱ类肽结合和 CD4+ T 细胞表位预测进行了评估。在表位预测方面，Predivac 优于三种可用的泛特异性方法（提供最高的特异性）。一个重要的发现是该方法在识别免疫优势和混杂 CD4+ T 细胞表位方面的准确性很高，这些表位在基于表位的疫苗设计中起着至关重要的作用。
全面的 HLA Ⅱ类等位基因覆盖以及在识别免疫优势 CD4+ T 细胞表位方面的高特异性使 Predivac 成为在遗传异质性人群中辅助基于表位的疫苗设计的有价值的工具。该工具可在以下网址获得：http://predivac.biosci.uq.edu.au/。
