Download MendeleyStructures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope.
Li, X., Zhang, L., Liu, Y., Ma, L., Zhang, N., Xia, C.(2020) J Biol Chem 295: 5292-5306
- PubMed: 32152225
- DOI: https://doi.org/10.1074/jbc.RA120.012713
- Primary Citation of Related Structures:
6IRL, 6KX9 - PubMed Abstract:
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-β2m (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 Å 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.
Organizational Affiliation:
Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, People's Republic of China; School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, People's Republic of China.
