Journal
NATURE IMMUNOLOGY
Volume 21, Issue 2, Pages 199-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-019-0581-0
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Funding
- National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS
- UM-1 grant for the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery [AI100645]
- National Institutes of Health [R21-AI100696, CHAVI-AI0678501, R01AI127877, R01AI130398]
- MRC Programme [MR/ K012037]
- MRC [MR/K012037/1] Funding Source: UKRI
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A subset of HIV-infected individuals can develop broadly neutralizing antibodies. Boyd and colleagues studied such HIV-infected individuals and found significant perturbations in their antibody repertoires, including increased frequencies of B cells expressing antibodies with features associated with autoreactivity. A goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and polyreactivity. A subset of HIV-infected individuals develops such antibodies, but it is unclear whether this reflects systematic differences in their antibody repertoires or is a consequence of rare stochastic events involving individual clones. We sequenced antibody heavy-chain repertoires in a large cohort of HIV-infected individuals with bNAb responses or no neutralization breadth and uninfected controls, identifying consistent features of bNAb repertoires, encompassing thousands of B cell clones per individual, with correlated T cell phenotypes. These repertoire features were not observed during chronic cytomegalovirus infection in an independent cohort. Our data indicate that the development of numerous B cell lineages with antibody features associated with autoreactivity may be a key aspect in the development of HIV neutralizing antibody breadth.
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