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Structures Of The Mhc-I Molecule Bf2*1501 Disclose The Preferred Presentation Of An H5N1 Virus-Derived Epitope

文献类型： 外文期刊

作者： Li, XY; Zhang, LJ; Liu, YJ; Ma, LZ; Zhang, NZ; Xia, C

作者机构：

关键词： Major Histocompatibility Complex (Mhc); Epitope Mapping; Crystal Structure; Influenza Virus; T-Cell Biology; Chicken; Cytotoxic T Lymphocyte (Ctl); Vaccine Development

期刊名称： JOURNAL OF BIOLOGICAL CHEMISTRY

ISSN： 0021-9258

年卷期： 2020 年 295 卷 16 期

页码：

收录情况： JCR（2021版） ; EI（2021版）

摘要： Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8(+) T-cell?mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I??2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV?PA(123?130). We determined the structure of the BF2*1501?PA(123?130) complex at 2.1 ? resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA(123?130) epitope in the chicken B15 lineage. Conformational characteristics of the PA(123?130) epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8(+) T cells specific for the HPAIV?PA(123?130) epitope in peptide-immunized chickens indicated that a repertoire of CD8(+) T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA(123?130) epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.

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