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

被引:9
作者
Blazkova, Jana [1 ]
Refsland, Eric W. [1 ]
Clarridge, Katherine E. [1 ]
Shi, Victoria [1 ]
Justement, J. Shawn [1 ]
Huiting, Erin D. [1 ]
Gittens, Kathleen R. [2 ]
Chen, Xuejun [3 ]
Schmidt, Stephen D. [3 ]
Liu, Cuiping [3 ]
Doria-Rose, Nicole [3 ]
Mascola, John R. [3 ]
Heredia, Alonso [4 ]
Moir, Susan [1 ]
Chun, Tae-Wook [1 ]
机构
[1] NIAID, Lab Immunoregulat, 9000 Rockville Pike, Bethesda, MD 20892 USA
[2] NIAID, Crit Care Med Dept, Clin Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] NIAID, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA
[4] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA
关键词
POTENT; AUTOREACTIVITY; ACTIVATION; RESERVOIRS; OBSTACLES; VIREMIA; HUMANS;
D O I
10.1172/JCI125955
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:4832 / 4837
页数:6
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