NDLI: Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses

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Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses

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Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sun, Yeping Liu, Jun Yang, Meng Gao, Feng Zhou, Jianfang Kitamura, Yoshihiro Gao, Bin Tien, Po Shu, Yuelong Iwamoto, Aikichi Chen, Zhu Gao, George F.
Description	Author Affiliation: Sun Y ( CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.)
Abstract	The haemagglutinin (HA) glycoprotein of influenza A virus is a major antigen that initiates 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. By using in silico prediction, in vitro refolding and a T2 cell-binding assay, followed by immunization of HLA-A2.1/K(b) 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 peripheral blood mononuclear cells of HLA-A0201-positive patients who had 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 and 2.2 A 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 differences, despite their nearly identical sequences. These results provide implications for the discovery of diagnostic markers and the design of novel influenza vaccines.
File Format	HTM / HTML
ISSN	00221317
e-ISSN	14652099
DOI	10.1099/vir.0.016766-0
Journal	Journal of General Virology
Issue Number	Pt 4
Volume Number	91
Language	English
Publisher	Microbiology Society
Publisher Date	2010-04-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Interferon-gamma Research Support, Non-u.s. Gov't Immunization X-ray Diffraction Hla-a Antigens Peptides Discipline Virology T-lymphocytes, Cytotoxic Mice, Transgenic Biosynthesis Hemagglutinin Glycoproteins, Influenza Virus Protein Folding Hla-a2 Antigen Chemistry Immunology Animals Influenza, Human Epitopes, T-lymphocyte Mice Influenza A Virus, H5n1 Subtype
Content Type	Text
Resource Type	Article
Subject	Virology

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Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses

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