tetano
Editor, Senior Moderator
Cell Rep
. 2023 Nov 15;42(11):113410.
doi: 10.1016/j.celrep.2023.113410. Online ahead of print. Stringent and complex sequence constraints of an IGHV1-69 broadly neutralizing antibody to influenza HA stem
Qi Wen Teo[SUP] 1 [/SUP], Yiquan Wang[SUP] 2 [/SUP], Huibin Lv[SUP] 1 [/SUP], Timothy J C Tan[SUP] 3 [/SUP], Ruipeng Lei[SUP] 2 [/SUP], Kevin J Mao[SUP] 2 [/SUP], Nicholas C Wu[SUP] 4 [/SUP]
Affiliations
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 reveals 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 demonstrate that the CDR H3 sequences from many other IGHV1-69 antibodies, including those to the HA stem, are 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.
Keywords: CP: Immunology; antibody; broadly neutralizing antibodies; hemagglutinin; high-throughput experiments; influenza virus; next-generation sequencing; sequence motifs; yeast display
. 2023 Nov 15;42(11):113410.
doi: 10.1016/j.celrep.2023.113410. Online ahead of print. Stringent and complex sequence constraints of an IGHV1-69 broadly neutralizing antibody to influenza HA stem
Qi Wen Teo[SUP] 1 [/SUP], Yiquan Wang[SUP] 2 [/SUP], Huibin Lv[SUP] 1 [/SUP], Timothy J C Tan[SUP] 3 [/SUP], Ruipeng Lei[SUP] 2 [/SUP], Kevin J Mao[SUP] 2 [/SUP], Nicholas C Wu[SUP] 4 [/SUP]
Affiliations
- PMID: 37976161
- DOI: 10.1016/j.celrep.2023.113410
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 reveals 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 demonstrate that the CDR H3 sequences from many other IGHV1-69 antibodies, including those to the HA stem, are 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.
Keywords: CP: Immunology; antibody; broadly neutralizing antibodies; hemagglutinin; high-throughput experiments; influenza virus; next-generation sequencing; sequence motifs; yeast display