EMD-44112

Single-particle
3.09 Å
EMD-44112 Deposition: 15/03/2024
Map released: 11/12/2024
Last modified: 11/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-44112

Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal antibody Fab 43_S0008

EMD-44112

Single-particle
3.09 Å
EMD-44112 Deposition: 15/03/2024
Map released: 11/12/2024
Last modified: 11/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Influenza A virus, Mus sp., Homo sapiens
Sample: Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal antibody Fab 43_S0008
Fitted models: 9b2m (Avg. Q-score: 0.377)

Deposition Authors: Torrents de la Pena A, de Paiva Froes Rocha R, Ward AB, Ataca S, Kanekiyo M
Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem.
PUBMED: 39580804
DOI: doi:10.1016/j.celrep.2024.114990
ISSN: 2211-1247
Abstract:
Antibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic mice that reproduce the human IGHV1-6901 germline-encoded antibody response to the conserved stem epitope on group 1 hemagglutinin (HA) of influenza A virus to show that this germline-endowed response can be overridden by a subdominant yet cross-group reactive public antibody response. Immunization with a non-cognate group 2 HA stem enriched B cells harboring the IGHD3-9 gene, thereby switching from IGHV1-69- to IGHD3-9-encoded motif-dependent epitope recognition. These IGHD3-9 antibodies bound, neutralized, and conferred cross-group protection in mice against influenza A viruses. A cryoelectron microscopy (cryo-EM) structure of an IGHD3-9 antibody resembled the human broadly neutralizing antibody FI6v3, which uses IGHD3-9. Together, our findings offer insights into vaccine regimens that engage an immunoglobulin repertoire with broader cross-reactivity to influenza A viruses.