Anti–influenza H7 human antibody targets antigenic site in hemagglutinin head domain interface
Jinhui Dong, Iuliia Gilchuk, Sheng Li, Ryan Irving, Matthew T. Goff, Hannah L. Turner, Andrew B. Ward, Robert H. Carnahan, James E. Crowe Jr.
Jinhui Dong, Iuliia Gilchuk, Sheng Li, Ryan Irving, Matthew T. Goff, Hannah L. Turner, Andrew B. Ward, Robert H. Carnahan, James E. Crowe Jr.
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Concise Communication Immunology Infectious disease

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

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.

Authors

Jinhui Dong, Iuliia Gilchuk, Sheng Li, Ryan Irving, Matthew T. Goff, Hannah L. Turner, Andrew B. Ward, Robert H. Carnahan, James E. Crowe Jr.

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Figure 3

Crystal structure and detailed interactions between Fab H7-200 and H7N9 SH13 HA1.

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Crystal structure and detailed interactions between Fab H7-200 and H7N9 ...
All protein components of the Ab-Ag complex are shown in a cartoon representation. The HA1 domain is shown in green, the H7-200 Fab heavy chain in cyan, and the light chain in magenta. (A) Individual CDRs of Fab H7-200, together with the influenza HA1 190 helix of HA1, are labeled. Left and right panels show side and top views of the complex structure. Principal and secondary antigenic sites are indicated with yellow ovals. (B) The principal antigenic site on H7N9 HA recognized by Fab H7-200, including residues Q163, N199–L201, and N208–S216, interacts with the Fab H7-200 heavy-chain strands C′ and C′′, CDRH2, CDRH3, CDRH1, and CDRL3. Residues involved in the Ab-Ag interaction are shown in stick representation. Hydrogen bonds are represented by dashed yellow lines. H7N9 HA residues are labeled in black, residues from Fab H7-200 heavy chain in red, and those from the light chain in blue. Fab H7-200 residues were numbered using the Kabat numbering system. (C) The secondary antigenic site on H7N9 HA recognized by Fab H7-200, consisting of residues K101, V103, I182, H184, D231, and H233, interacts with the tip of the CDRH3 loop of Fab H7-200. (D) Sequence alignment of antigenic sites of several major H7 influenza and H15N9 viruses recognized by Fab H7-200 and H1N1, H3N2, H5N1, and H10N8 viruses. Antigenic residues are highlighted with brown rectangles, and important residues for Ab-Ag binding in the crystal structure of the Ab-Ag complex are marked with red bars. The first residues of the sequence segments are numbered. Sequence alignment was performed with the multiple sequence alignment software Muscle (17), and the alignment figure was made with the sequence alignment editing software Aline (18).