Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals
| Autor: | Cuiping Liu, Eric W. Refsland, Victoria Shi, Jana Blazkova, Tae-Wook Chun, Stephen D. Schmidt, John R. Mascola, Susan Moir, Erin D Huiting, J. Shawn Justement, Kathleen R. Gittens, Xuejun Chen, Alonso Heredia, Nicole A. Doria-Rose, Katherine E Clarridge |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Glycan Glycosylation CD8-Positive T-Lymphocytes HIV Antibodies Virus 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antibody Specificity Bystander effect Humans Glucans biology Concise Communication Degranulation General Medicine Virology Antibodies Neutralizing Killer Cells Natural 030104 developmental biology Viral replication chemistry 030220 oncology & carcinogenesis biology.protein Female Antibody CD8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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