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

• DOI: 10.1099/vir.0.016766-0
• Publication Date: 2009-12-03T04:07:48Z
• Authors: Y. Sun; J. Liu; M. Yang; F. Gao; J. Zhou; Y. Kitamura; B. Gao; P. Tien; Y. Shu; A. Iwamoto; Z. Chen; G. F. Gao
• Keywords: CTL*

The haemagglutinin (HA) glycoprotein of influenza A virus is a major antigen that initiates humoral immunity against infection; however, the cellular immune response HA poorly understood. Furthermore, HA-derived cytotoxic T-lymphocyte (CTL) epitopes are relatively rare in comparison to other internal gene products. Here, CTL serotype H5 protein were screened. By using silico prediction, vitro refolding and T2 cell-binding assay, followed by immunization HLA-A2.1/Kb transgenic mice, an HLA-A*0201-restricted decameric epitope, RI-10 (H5 HA205–214, RLYQNPTTYI), was shown elicit robust epitope-specific response. In addition, its variant, KI-10 (KLYQNPTTYI), also demonstrated be able induce higher than dominant epitope GL-9 (GILGFVFTL) peripheral blood mononuclear cells HLA-A*0201-positive patients who had recovered from H5N1 infection. crystal structures RI-10–HLA-A*0201 KI-10–HLA-A*0201 complexes determined at 2.3 2.2 Å resolution, respectively, showing typical epitopes. conformations antigen-presenting grooves two show significant differences, despite their nearly identical sequences. These results provide implications for discovery diagnostic markers design novel vaccines.