Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from H5N1 subtype of influenza A viruses.----中国科学院微生物研究所

科研成果

论文题目:	Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from H5N1 subtype of influenza A viruses.
作者:	Yeping Sun, Jun Liu, Meng Yang, Feng Gao, Jianfang Zhou, Yoshihiro Kitamura, Bin Gao, Po Tien, Yuelong Shu, Aikichi Iwamoto, Zhu Chen, George F. Gao*
联系作者:	高福
刊物名称:	Joural of General Virology
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年份:	2010
影响因子:	3.260
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摘要:	The hemagglutinin (HA) glycoprotein of influenza A virus is a major antigen that initiates the humoral immunity against infection, however, the cellular immune response against HA is poorly understood. Furthermore HA-derived cytotoxic T lymphocyte (CTL) epitopes are relatively rare in comparison to other internal gene products. Here CTL epitopes of the HA serotype H5 protein were screened. Using in silico prediction, in vitro refolding and a T2 cell binding assay, followed by immunization of HLA-A2.1/Kb transgenic mice, an HLA-A0201-restricted decameric epitope, RI-10 (H5 HA205-214, RLYQNPTTYI), was shown to elicit a robust CTL-epitope specific response. In addition, RI-10 and its variant, KI-10 (KLYQNPTTYI), were also demonstrated to be able to induce a higher CTL-epitope specific response than the influenza A virus dominant CTL epitope GL-9 (GILGFVFTL) in PBMCs of HLA-A0201-positive patients recovered from H5N1 virus infection. Furthermore, the crystal structures of RI-10-HLA-A0201 and KI-10-HLA-A0201 complexes were determined at 2.3 Å and 2.2 Å resolution, respectively, showing typical HLA-A*0201-restricted epitopes. The conformations of RI-10 and KI-10 in the antigen presenting grooves in crystal structures of the two complexes show significant difference despite of their nearly identical sequences. These results provide implications for the discovery of diagnostic marker and the design of novel influenza vaccines.