Format

Send to

Choose Destination
J Biol Chem. 2020 Mar 9. pii: jbc.RA120.012713. doi: 10.1074/jbc.RA120.012713. [Epub ahead of print]

Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope.

Author information

1
China Agricultural University, China.
2
Department of Microbiology and Immunology, China Agricultural University, China.

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 (SPF) pMHC-I (pBF2*1501), we identified a highly conserved HPAIV H5N1 CTL epitope, named HPAIV-PA123-130 We determined the structure of the BF2*1501-PA123-130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly conserved PA123-130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123-130 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-PA123-130 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 PA123-130 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.

KEYWORDS:

H5N1; T-cell biology; chicken; crystal structure; cytotoxic T lymphocyte (CTL); epitope mapping; influenza virus; major histocompatibility complex (MHC); vaccine development

PMID:
32152225
DOI:
10.1074/jbc.RA120.012713
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center