Molecular docking analysis of 2009-H1N1 and 2004-H5N1 influenza virus HLA-B*4405-restricted HA epitope candidates

implications for TCR cross-recognition and vaccine development.

Chinh T T Su, Christian Schönbach, Chee Keong Kwoh

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The pandemic 2009-H1N1 influenza virus circulated in the human population and caused thousands deaths worldwide. Studies on pandemic influenza vaccines have shown that T cell recognition to conserved epitopes and cross-reactive T cell responses are important when new strains emerge, especially in the absence of antibody cross-reactivity. In this work, using HLA-B*4405 and DM1-TCR structure model, we systematically generated high confidence conserved 2009-H1N1 T cell epitope candidates and investigated their potential cross-reactivity against H5N1 avian flu virus. Molecular docking analysis of differential DM1-TCR recognition of the 2009-H1N1 epitope candidates yielded a mosaic epitope (KEKMNTEFW) and potential H5N1 HA cross-reactive epitopes that could be applied as multivalent peptide towards influenza A vaccine development. Structural models of TCR cross-recognition between 2009-H1N1 and 2004-H5N1 revealed steric and topological effects of TCR contact residue mutations on TCR binding affinity. The results are novel with regard to HA epitopes and useful for developing possible vaccination strategies against the rapidly changing influenza viruses. Yet, the challenge of identifying epitope candidates that result in heterologous T cell immunity under natural influenza infection conditions can only be overcome if more structural data on the TCR repertoire become available.

Original languageEnglish
JournalBMC Bioinformatics
Volume14 Suppl 2
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Molecular Docking Simulation
H5N1 Subtype Influenza A Virus
Molecular Docking
Epitopes
HLA-B Antigens
Vaccines
Vaccine
Influenza
Orthomyxoviridae
Viruses
Virus
T-cells
Reactivity
Influenza Vaccines
Pandemics
T-Lymphocytes
Vaccination
Structural Model
Immunity
H1N1 Subtype Influenza A Virus

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics
  • Structural Biology

Cite this

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title = "Molecular docking analysis of 2009-H1N1 and 2004-H5N1 influenza virus HLA-B*4405-restricted HA epitope candidates: implications for TCR cross-recognition and vaccine development.",
abstract = "The pandemic 2009-H1N1 influenza virus circulated in the human population and caused thousands deaths worldwide. Studies on pandemic influenza vaccines have shown that T cell recognition to conserved epitopes and cross-reactive T cell responses are important when new strains emerge, especially in the absence of antibody cross-reactivity. In this work, using HLA-B*4405 and DM1-TCR structure model, we systematically generated high confidence conserved 2009-H1N1 T cell epitope candidates and investigated their potential cross-reactivity against H5N1 avian flu virus. Molecular docking analysis of differential DM1-TCR recognition of the 2009-H1N1 epitope candidates yielded a mosaic epitope (KEKMNTEFW) and potential H5N1 HA cross-reactive epitopes that could be applied as multivalent peptide towards influenza A vaccine development. Structural models of TCR cross-recognition between 2009-H1N1 and 2004-H5N1 revealed steric and topological effects of TCR contact residue mutations on TCR binding affinity. The results are novel with regard to HA epitopes and useful for developing possible vaccination strategies against the rapidly changing influenza viruses. Yet, the challenge of identifying epitope candidates that result in heterologous T cell immunity under natural influenza infection conditions can only be overcome if more structural data on the TCR repertoire become available.",
author = "Su, {Chinh T T} and Christian Sch{\"o}nbach and Kwoh, {Chee Keong}",
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