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Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses
- Source :
- Cell Discovery, Vol 5, Iss 1, Pp 1-16 (2019), Cell Discovery
- Publication Year :
- 2020
- Publisher :
- The Francis Crick Institute, 2020.
-
Abstract
- The isolation of human monoclonal antibodies with broadly neutralizing breadth can provide a promising countermeasure for influenza A viruses infection. Most broadly neutralizing antibodies against influenza A viruses bind to the conserved stem region or the receptor-binding cavity of hemagglutinin and the interaction is dominated by the heavy chain. The light chain, however, contributes few or no direct contacts to the antigen. Here we report an H3-clade neutralizing human monoclonal antibody, AF4H1K1, which recognizes the hemagglutinin glycoproteins of all group 2 influenza A viruses. This human monoclonal antibody has been obtained through the screening by pairing different heavy and light chains from an H7N9-infected patient based on the next-generation sequencing technology. Further structural studies revealed that light chains modulate the neutralizing spectrum by affecting the local conformation of heavy chains, instead of direct interaction with the antigen. These findings provide important clues to understand the molecular basis of light chains in antigen recognition and to explore the strategies in particular of the use of light chain modification to develop broadly protective monoclonal antibodies against influenza A viruses and other emerging viruses.
- Subjects :
- medicine.drug_class
Hemagglutinin (influenza)
Infectious Disease
Monoclonal antibody
Immunoglobulin light chain
Biochemistry
Article
03 medical and health sciences
0302 clinical medicine
Antigen
Ecology,Evolution & Ethology
Genetics
medicine
lcsh:QH573-671
Molecular Biology
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Heavy chain
biology
lcsh:Cytology
Chemistry
Influenza a
Cell Biology
Virology
biology.protein
Antibody
Glycoprotein
030217 neurology & neurosurgery
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell Discovery, Vol 5, Iss 1, Pp 1-16 (2019), Cell Discovery
- Accession number :
- edsair.doi.dedup.....9767fedbbe56a5b6655158fc30fc0934
- Full Text :
- https://doi.org/10.25418/crick.11498766.v1