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Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals
Jana Blazkova, … , Susan Moir, Tae-Wook Chun
Jana Blazkova, … , Susan Moir, Tae-Wook Chun
Published October 7, 2019
Citation Information: J Clin Invest. 2019;129(11):4832-4837. https://doi.org/10.1172/JCI125955.
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Concise Communication AIDS/HIV Immunology

Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals

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Abstract

A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans. However, the degree and extent to which such bNAbs interact with primary lymphocytes have not been fully delineated. Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals. Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation. In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death. Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.

Authors

Jana Blazkova, Eric W. Refsland, Katherine E. Clarridge, Victoria Shi, J. Shawn Justement, Erin D. Huiting, Kathleen R. Gittens, Xuejun Chen, Stephen D. Schmidt, Cuiping Liu, Nicole Doria-Rose, John R. Mascola, Alonso Heredia, Susan Moir, Tae-Wook Chun

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Figure 1

Binding of bNAbs to a chronically HIV-infected cell line and lymphocytes of uninfected individuals.

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Binding of bNAbs to a chronically HIV-infected cell line and lymphocytes...
(A) Binding of bNAbs to an uninfected (CEM-NKR-CCR5, light gray) and a chronically HIV-infected cell line (CEM-IIIB, dark gray). Levels of binding of bNAbs and IgG (negative control) to B cells (B), CD4+ T cells (C), and CD8+ T cells (D) in PBMCs from HIV-negative donors. (E) IgG and PGT121 binding to unstimulated and anti-CD3–stimulated CD4+ T cells. Binding of PGT121 (F), 10-1074 (G), and PG16 (H) to B cells, and CD4+ and CD8+ T cells in PBMCs from HIV-uninfected individuals prior to (day 0, D0) and 2 days following stimulation with anti-CD3 (D2). The median values are shown as gray bars. Statistical significance was tested with Wilcoxon’s matched-pairs signed-rank test. ***P < 0.001.
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