ArticleJournal of virology2011
Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 61 citations in OpenAlex.
- The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies.PLoS pathogens · 2013Trial
- Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.medRxiv : the preprint server for health sciences · 2026Article
- Safety and immunogenicity of an HIV envelope trimer immunogen that elicits CD4 binding site neutralizing antibody precursors (HVTN 300).medRxiv : the preprint server for health sciences · 2026Article
- Germline-Targeting Strategies to Induce bNAbs against HIV-1.Current HIV research · 2026Review
- Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025Article
- An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.Cell host & microbe · 2024Article
- Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity.Cell reports · 2023Article
- Widespread impact of immunoglobulin V gene allelic polymorphisms on antibody reactivity.bioRxiv : the preprint server for biology · 2023Article
- Molecular analysis of a public cross-neutralizing antibody response to SARS-CoV-2.bioRxiv : the preprint server for biology · 2022Article
- Strategies for induction of HIV-1 envelope-reactive broadly neutralizing antibodies.Journal of the International AIDS Society · 2021Review
- Cross-Reactivity to Kynureninase Tolerizes B Cells That Express the HIV-1 Broadly Neutralizing Antibody 2F5.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Minding the gap: The impact of B-cell tolerance on the microbial antibody repertoire.Immunological reviews · 2019Review
- Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design.Retrovirology · 2018Review
- Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing.Frontiers in immunology · 2018Review
- Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.Science immunology · 2017Article
- Humanized Immunoglobulin Mice: Models for HIV Vaccine Testing and Studying the Broadly Neutralizing Antibody Problem.Advances in immunology · 2017Review
- Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development.Immunological reviews · 2017Review
- Human Ig knockin mice to study the development and regulation of HIV-1 broadly neutralizing antibodies.Immunological reviews · 2017Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Genetic factors, as well as antigenic stimuli, can influence antibody repertoire formation. Moreover, the affinity of antigen for unmutated naïve B cell receptors determines the threshold for activation of germinal center antibody responses. The gp41 2F5 broadly neutralizing antibody (bNAb) uses the V(H)2-5 gene, which has 10 distinct alleles that use either a heavy-chain complementarity-determining region 2 (HCDR2) aspartic acid (D(H54)) or an HCDR2 asparagine (N(H54)) residue. The 2F5 HCDR2 D(H54) residue has been shown to form a salt bridge with gp41 (665)K; the V(H)2-5 germ line allele variant containing N(H54) cannot do so and thus should bind less avidly to gp41. Thus, the induction of 2F5 bNAb is dependent on both genetic and structural factors that could affect antigen affinity of unmutated naïve B cell receptors. Here, we studied allelic variants of the V(H)2-5 inferred germ line forms of the HIV-1 gp41 bNAb 2F5 for their antigen binding affinities to gp41 linear peptide and conformational protein antigens. Both V(H)2-5 2F5 inferred germ line variants bound to gp41 peptides and protein, including the fusion intermediate protein mimic, although more weakly than the mature 2F5 antibody. As predicted, the affinity of the N(H54) variant for fusion-intermediate conformation was an order of magnitude lower than that of the D(H54) V(H)2-5 germ line antibody, demonstrating that allelic variants of 2F5 germ line antibodies differentially bind to gp41. Thus, these data demonstrate a genetically determined trait that may affect host responses to HIV-1 envelope epitopes recognized by broadly neutralizing antibodies and has implications for unmutated ancestor-based immunogen design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.