| 论文题目: | Differential structural dynamics and antigenicity of two similar influenza H5N1 virus HA-specific HLA-A*0201-restricted CLT epitopes |
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| 作者: | Sun Yeping* Liu Qian. |
| 联系作者: | |
| 刊物名称: | Rsc Advances |
| 期: | 5 |
| 卷: | 3 |
| 页: | 2318-2327 |
| 年份: | 2015 |
| 影响因子: | 3.708 |
| 论文下载: | 下载地址 |
| 摘要: | The presentation of viral peptides by major histocompatibility complex (MHC) molecules for T cell receptor (TCR) recognition is the central event in the development of T cell immunity against viruses. Molecular dynamics (MD) simulation is a powerful tool that is able to provide dynamic information, rather than a static view, of the mechanisms of peptide presentation in the antigen binding grooves of MHCs. In this paper, MD simulations are presented for two influenza H5N1 virus HA-specific cytotoxic T lymphocyte (CTL) epitopes, RI-10 (RLYQNPTTYI) and KI-10 (KLYQNPTTYI), in complex with HLA-A*0201. Although the amino acid sequence difference between RI-10 and KI-10 is slight, the structural dynamics of the two peptides were found to differ substantially. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) calculations, and the thermal stability of the two complexes determined from their circular dichroism (CD) spectra, suggested that RI-10 had a higher binding free energy to HLA-A*0201 than KI-10. Furthermore, the structural fluctuation of the RI-10-HLA-A*0201 complex was found to be significantly lower than that of KI-10-HLA-A*0201. The distinctive salt bridges formed between Arg1 of RI-10 with Glu63 of HLA-A*0201 and the stronger hydrogen bond network may contribute to different structural dynamics between the two pMHC complexes through dynamic allosteric interaction mechanisms. RI-10-containing H5N1 virus strains isolated from Chinese patients are much less prevalent than KI-10-containing strains; this correlates with the higher antigenic potency of RI-10 in comparison to KI-10, as demonstrated in HLA-A*0201/K-b transgenic mice immunized with the two peptides. |
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