Anti-influenza H7 human antibody targets antigenic site in hemagglutinin head domain interface

J Clin Invest. 2020 Sep 1;130(9):4734-4739. doi: 10.1172/JCI136032.

Abstract

Although broadly protective, stem-targeted Abs against the influenza A virus hemagglutinin (HA) have been well studied, very limited information is available on Abs that broadly recognize the head domain. We determined the crystal structure of the HA protein of the avian H7N9 influenza virus in complex with a pan-H7, non-neutralizing, protective human Ab. The structure revealed a B cell epitope in the HA head domain trimer interface (TI). This discovery of a second major protective TI epitope supports a model in which uncleaved HA trimers exist on the surface of infected cells in a highly dynamic state that exposes hidden HA head domain features.

Keywords: B cells; Immunoglobulins; Immunology; Infectious disease; Influenza.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Video-Audio Media

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / chemistry*
  • Antibodies, Viral / immunology
  • Epitopes, B-Lymphocyte / chemistry*
  • Epitopes, B-Lymphocyte / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Influenza A Virus, H7N1 Subtype / chemistry*
  • Influenza A Virus, H7N1 Subtype / immunology
  • Mice
  • Protein Domains
  • Protein Multimerization

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes, B-Lymphocyte
  • Hemagglutinin Glycoproteins, Influenza Virus
  • hemagglutinin, avian influenza A virus