Mucosal immunology, 2009-09, Vol.2 (5), p.412-426
2009
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- Autor(en) / Beteiligte
- Titel
- HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG-seronegative individuals block HIV-1 epithelial transcytosis and neutralize CD4 cell infection: an IgA gene and functional analysis
- Ist Teil von
- Mucosal immunology, 2009-09, Vol.2 (5), p.412-426
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2009
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- AIDS is mainly a sexually transmitted disease, and accordingly, mucosal tissues are the primary sites of natural human immunodeficiency virus type-1 (HIV-1) transmission. Mucosal immunoglobulin A (IgA) antibody specific for HIV-1 envelope gp41 subunit is one correlate of protection in individuals who are highly sexually exposed to HIV-1 but remain persistently IgG seronegative (HEPS). Understanding these peculiar IgAs at the gene and functional level is possible only with monoclonal IgAs. We have constructed a mucosal Fab IgA library from HEPS and have characterized a series of HIV-1 IgAs specific for gp41 that, in vitro, are transcytosis-blocking and infection-neutralizing. Characterization of their IgA genes shows that Fab specific for the gp41 membrane-proximal region harbors a long heavy-chain CDR3 loop (CDRH3) similar to the two broadly neutralizing IgG monoclonal antibodies, 2F5 and 4E10. Furthermore, the selected Fab IgA shows extensive somatic mutations that cluster in the CDR regions, indicating that affinity maturation due to an antigen-driven process had occurred in HEPS individuals, presumably upon multiple exposures to HIV. This analysis of HEPS monoclonal IgA gives a unique opportunity to correlate an antibody function (resistance to a pathogen in vivo) with an antibody gene. Such neutralizing monoclonal IgAs could be used in microbicide formulation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1933-0219eISSN: 1935-3456DOI: 10.1038/mi.2009.89Titel-ID: cdi_hal_primary_oai_HAL_pasteur_00595475v1
- Format
- –
- Schlagworte
- Adult, Amino Acid Sequence, Antibodies, Monoclonal, Antibodies, Monoclonal - genetics, Antibodies, Monoclonal - immunology, Antibodies, Monoclonal - isolation & purification, CD4-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - virology, Cervix Uteri, Cervix Uteri - immunology, Conserved Sequence, Environmental Exposure, Female, Gene Rearrangement, B-Lymphocyte, HIV Antibodies, HIV Antibodies - genetics, HIV Antibodies - immunology, HIV Antibodies - isolation & purification, HIV Envelope Protein gp41, HIV Envelope Protein gp41 - immunology, HIV Infections, HIV Infections - immunology, HIV Infections - prevention & control, HIV Seronegativity, HIV Seronegativity - immunology, HIV-1, HIV-1 - immunology, HIV-1 - physiology, Humans, Immunity, Innate, Immunity, Innate - immunology, Immunoglobulin A, Secretory, Immunoglobulin A, Secretory - genetics, Immunoglobulin A, Secretory - immunology, Immunoglobulin A, Secretory - isolation & purification, Immunoglobulin Fab Fragments, Immunoglobulin Fab Fragments - genetics, Immunoglobulin Fab Fragments - immunology, Life Sciences, Microbiology and Parasitology, Molecular Sequence Data, Mucous Membrane, Mucous Membrane - immunology, Peptide Fragments, Peptide Fragments - immunology, Peptide Library, Sequence Alignment, Sequence Homology, Sexual Partners, Vagina, Vagina - immunology, Virus Internalization