Dhiman Gourav, Lohia Neha, Jain Sahil, Baranwal Manoj
Department of Biotechnology, Thapar University, Bhadson Road, Patiala, Punjab, India.
Microbiol Immunol. 2016 Sep;60(9):646-52. doi: 10.1111/1348-0421.12436.
The concept of peptide-based vaccines against cancer has made noteworthy progress. Metadherin (MTDH) overexpression and its role in the development of diverse cancers make it an attractive target for cancer immunotherapy. In the current study, six different T cell epitope prediction tools were run to identify MTDH peptides with multiple immunogenic regions. Further, molecular docking was performed to assess HLA-peptide binding interactions. Nine and eleven peptides fragments containing multiple CD8 (+) and CD4 (+) T-cell epitopes, ranging from 9 to 20 amino acids, respectively, were obtained using a consensus immunoinformatics approach. The three peptides that were finally identified as having overlapping CD4 (+) and CD8 (+) T- cell epitopes are ARLREMLSVGLGFLRTELG, FLLGYGWAAACAGAR, YIDDEWSGLNGLSSADP. These peptides were found to not only have multiple T cell epitopes but also to have binding affinity with wide HLA molecules. A molecular docking study revealed that the predicted immunogenic peptides (with single or multiple T cell epitopes) of MTDH have comparable binding energies with naturally bound peptides for both HLA classes I and II. Thus, these peptides have the potential to induce immune responses that could be considered for developing synthetic peptide vaccines against multiple cancers.
基于肽的抗癌疫苗概念已取得显著进展。Metadherin(MTDH)的过表达及其在多种癌症发展中的作用使其成为癌症免疫治疗的一个有吸引力的靶点。在本研究中,运行了六种不同的T细胞表位预测工具,以识别具有多个免疫原性区域的MTDH肽。此外,进行了分子对接以评估HLA-肽结合相互作用。使用共识免疫信息学方法分别获得了九个和十一个含有多个CD8(+)和CD4(+)T细胞表位的肽片段,其长度分别为9至20个氨基酸。最终确定的具有重叠CD4(+)和CD8(+)T细胞表位的三个肽是ARLREMLSVGLGFLRTELG、FLLGYGWAAACAGAR、YIDDEWSGLNGLSSADP。发现这些肽不仅具有多个T细胞表位,而且与多种HLA分子具有结合亲和力。分子对接研究表明,MTDH的预测免疫原性肽(具有单个或多个T细胞表位)与I类和II类HLA的天然结合肽具有相当的结合能。因此,这些肽有可能诱导免疫反应,可考虑用于开发针对多种癌症的合成肽疫苗。