Journal
CELL REPORTS
Volume 33, Issue 8, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.108430
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Funding
- Columbia University-Southern African Fogarty AIDS International Training and Research Program (AITRP) through the Fogarty International Center, National Institutes of Health [5 D43 TW000231]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [U01AI136677]
- South African Research Chairs Initiative of the Department of Science and Innovation (DSI)
- National Research Foundation (NRF) [98341]
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Institutes of Health (NIH)
- U.S. Department of Health and Human Services [AI51794]
- Poliomyelitis Research Foundation [16/23]
- University of the Witwatersrand Health Sciences Faculty Research Council grant
- South African NRF/DSI Centre of Excellence in HIV Prevention
- South African Medical Research Council (SAMRC)
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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 immunoglobuiin (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.
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