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A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
04:47

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies

Published on: February 23, 2018

H5N1 influenza binding and cell entry via human class II MHC, and blocking by cross-reactive antibodies

Taylor Pursell1,2, Artem Mikelov2, Oliver F Wirz2

  • 1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA.

Biorxiv : the Preprint Server for Biology
|August 1, 2026
PubMed

Insights

Emerging H5N1 avian influenza viruses bind human immune cells via MHC-II, independent of sialic acid. This interaction, influenced by host genetics, offers new therapeutic targets against H5N1 virus infections.

Area of Science:

  • Virology and Immunology
  • Molecular Biology
  • Genetics

Background:

  • Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses are causing a widespread, multi-species outbreak.
  • Influenza A viruses typically use sialic acid for cell entry, but some utilize major histocompatibility complex class II (MHC-II) molecules.

Purpose of the Study:

  • To investigate the cell entry mechanisms of emerging H5N1 clade 2.3.4.4b viruses.
  • To determine if these viruses can bind to human MHC-II molecules and mediate sialic acid-independent cell entry.
  • To explore the role of host genetic variation and pre-existing immunity in H5N1 infection susceptibility and potential therapeutic interventions.

Main Methods:

  • Analysis of hemagglutinin binding to human MHC-II HLA-DR.
  • Assessment of sialic acid-independent cell entry mediated by H5N1 clade 2.3.4.4b viruses.
  • Investigation of the impact of mammalian-adaptive substitutions on MHC-II binding.
  • Characterization of cross-reactive monoclonal antibodies for blocking HA-MHC-II interaction.

Main Results:

  • Emerging H5N1 clade 2.3.4.4b viruses bind human MHC-II HLA-DR and enter cells independently of sialic acid, unlike historical H5 lineages.
  • Hemagglutinin binding affinity varies with MHC-II expression and HLA-DR allelic variation, indicating host genetic influence on susceptibility.
  • Mammalian-adaptive mutations in the hemagglutinin reduce MHC-II binding, suggesting adaptation to human hosts remodels this interaction.
  • Monoclonal antibodies from H5N1-naive humans can block the hemagglutinin-MHC-II interaction.

Conclusions:

  • Contemporary H5N1 viruses utilize a novel receptor pathway involving human MHC-II for cell entry.
  • Host genetic diversity and pre-existing humoral immunity modulate H5N1 interactions, impacting viral host range and spillover risk.
  • The HA-MHC-II interaction presents a potential target for therapeutic interventions against H5N1 avian influenza.

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