Détail du document
Identifiant
oai:pubmedcentral.nih.gov:1035...
Sujet
ArticleAuteur
Teo, Qi Wen Wang, Yiquan Lv, Huibin Tan, Timothy J.C. Lei, Ruipeng Mao, Kevin J. Wu, Nicholas C.Langue
enEditeur
Cold Spring Harbor Laboratory
Catégorie
biorxiv
Année
2023
Date de référencement
19/07/2023
Mots clés
sequence light broadly neutralizing influenza antibodiesRésumé
IGHV1-69 is frequently utilized by broadly neutralizing influenza antibodies to the hemagglutinin (HA) stem.
These IGHV1-69 HA stem antibodies have diverse complementarity-determining region (CDR) H3 sequences.
Besides, their light chains have minimal to no contact with the epitope.
Consequently, sequence determinants that confer IGHV1-69 antibodies with HA stem specificity remain largely elusive.
Using high-throughput experiments, this study revealed the importance of light chain sequence for the IGHV1-69 HA stem antibody CR9114, which is the broadest influenza antibody known to date.
Moreover, we demonstrated that the CDR H3 sequences from many other IGHV1-69 antibodies, including those to HA stem, were incompatible with CR9114.
Along with mutagenesis and structural analysis, our results indicate that light chain and CDR H3 sequences coordinately determine the HA stem specificity of IGHV1-69 antibodies.
Overall, this work provides molecular insights into broadly neutralizing antibody responses to influenza virus, which have important implications for universal influenza vaccine development.
Teo, Qi Wen,Wang, Yiquan,Lv, Huibin,Tan, Timothy J.C.,Lei, Ruipeng,Mao, Kevin J.,Wu, Nicholas C., 2023, Stringent and complex sequence constraints of an IGHV1-69 broadly neutralizing antibody to influenza HA stem , Cold Spring Harbor Laboratory
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