Differential structural dynamics and antigenicity of two similar influenza H5N1 virus HA-specific HLA-A*0201-restricted CLT epitopes----中国科学院微生物研究所

科研成果

论文题目:	Differential structural dynamics and antigenicity of two similar influenza H5N1 virus HA-specific HLA-A*0201-restricted CLT epitopes
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:	3.907
论文下载:	http://pubs.rsc.org/en/Content/ArticleLanding/2015/RA/C4RA08874C#!divAbstract
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-A0201. 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-A0201 than KI-10. Furthermore, the structural fluctuation of the RI-10-HLA-A0201 complex was found to be significantly lower than that of KI-10-HLA-A0201. The distinctive salt bridges formed between Arg1 of RI-10 with Glu63 of HLA-A0201 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-A0201/K-b transgenic mice immunized with the two peptides.