Cell reports · 2020
Antibody Isotype Switching as a Mechanism to Counter HIV Neutralization Escape.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Scheepers Cathrine, Bekker Valerie, Anthony Colin, Richardson Simone I, Oosthuysen Brent, Moyo Thandeka, Kgagudi Prudence, Kitchin Dale, Nonyane Molati, York Talita, Mielke Dieter, Mabvakure Batsirai M, Sheng Zizhang, Lambson Bronwen E, Ismail Arshad, Garrett Nigel J, Abdool Karim Salim S, Shapiro Lawrence, Williamson Carolyn, Morris Lynn, Moore Penny L
Аннотация
Neutralizing antibodies (nAbs) to highly variable viral pathogens show remarkable diversification during infection, resulting in an "arms race" between virus and host. Studies of nAb lineages have shown how somatic hypermutation (SHM) in immunoglobulin (Ig)-variable regions enables maturing antibodies to neutralize emerging viral escape variants. However, the Ig-constant region (which determines isotype) can also influence epitope recognition. Here, we use longitudinal deep sequencing of an HIV-directed nAb lineage, CAP88-CH06, and identify several co-circulating isotypes (IgG3, IgG1, IgA1, IgG2, and IgA2), some of which share identical variable regions. First, we show that IgG3 and IgA1 isotypes are better able to neutralize longitudinal autologous viruses and epitope mutants than can IgG1. Second, detrimental class-switch recombination (CSR) events that resulted in reduced neutralization can be rescued by further CSR, which we term "switch redemption." Thus, CSR represents an additional immunological mechanism to counter viral escape from HIV-specific antibody responses.