Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), (ICMR), 1, Sathiyamoorthy Road, Chetpet, Chennai, 600031, Tamil Nadu, India.
Immunogenetics. 2012 Oct;64(10):767-72. doi: 10.1007/s00251-012-0635-z. Epub 2012 Jul 19.
Earlier studies have identified a large number of immunogenic epitopes in HIV-1. Efforts are required to prioritize these epitopes in order to identify the best candidates for formulating an effective multi-epitope vaccine for HIV. We modeled 155 known cytotoxic T lymphocyte epitopes of HIV-1 subtype C on the 3D structure of HLA-A0201, HLA-B2705, and HLA-B*5101 using MODPROPEP, as these alleles are known to be associated with resistance to HIV/slow progression to AIDS. Thirty-six epitopes were identified to bind to all the three HLA alleles with better binding affinity than the control peptides complexed with each HLA allele but not to any of the HLA alleles reported to be associated with susceptibility to HIV infection/rapid progression to disease. As increase in stability of the epitope-HLA complex results in increased immunogenicity, the short-listed epitopes could be suitable candidates for vaccine development. Twenty of the 36 epitopes were polyfunctional in nature adding to their immunological relevance for vaccine design. Further, 9 of the 20 polyfunctional epitopes were found to bind to all three resistance-associated HLA alleles using an additional method, adding worth to their potential as candidates for a vaccine formulation for HIV-1C.
早期研究已经确定了 HIV-1 中大量的免疫原性表位。需要努力对这些表位进行优先级排序,以确定用于制定针对 HIV 的有效多表位疫苗的最佳候选物。我们使用 MODPROPEP 在 HLA-A0201、HLA-B2705 和 HLA-B*5101 的 3D 结构上模拟了 155 个已知的 HIV-1 亚型 C 的细胞毒性 T 淋巴细胞表位,因为这些等位基因与对 HIV 的抗性/对 AIDS 的缓慢进展有关。鉴定出 36 个表位与所有三种 HLA 等位基因结合的亲和力均优于与每个 HLA 等位基因结合的对照肽,但不与任何报告与 HIV 感染易感性/疾病快速进展相关的 HLA 等位基因结合。由于表位-HLA 复合物的稳定性增加会导致免疫原性增加,因此被列入名单的表位可能是疫苗开发的合适候选物。这 36 个表位中有 20 个具有多功能性,这增加了它们在疫苗设计方面的免疫学相关性。此外,使用另一种方法发现 20 个多功能表位中的 9 个与所有三种耐药相关的 HLA 等位基因结合,这增加了它们作为 HIV-1C 疫苗制剂候选物的潜力。