Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular Cytotoxicity
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against H...
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doaj-6c8e44d393a342068ad7257350e95e402020-11-24T23:03:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.01033285094Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular CytotoxicityNicole F. Bernard0Nicole F. Bernard1Nicole F. Bernard2Nicole F. Bernard3Zahra Kiani4Zahra Kiani5Alexandra Tremblay-McLean6Alexandra Tremblay-McLean7Sanket A. Kant8Sanket A. Kant9Christopher E. Leeks10Christopher E. Leeks11Franck P. Dupuy12Research Institute of the McGill University Health Centre, Montreal, QC, CanadaDivision of Experimental Medicine, McGill University, Montreal, QC, CanadaChronic Viral Illness Service, McGill University Health Centre, Montreal, QC, CanadaDivision of Clinical Immunology, McGill University Health Centre, Montreal, QC, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC, CanadaDivision of Experimental Medicine, McGill University, Montreal, QC, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC, CanadaDivision of Experimental Medicine, McGill University, Montreal, QC, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC, CanadaDivision of Experimental Medicine, McGill University, Montreal, QC, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC, CanadaDivision of Experimental Medicine, McGill University, Montreal, QC, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC, CanadaImmunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present. Systems serology analyses implicated a broader range of Ab-dependent functions in protection from HIV infection, including but not limited to ADCC and Ab-dependent NK cell activation (ADNKA) for secretion of IFN-γ and CCL4 and expression of the degranulation marker CD107a. The existence of such correlations in the absence of bNAbs in the RV144 trial suggest that NK cells could be instrumental in protecting against HIV infection by limiting viral spread through Fc-mediated functions such as ADCC and the production of antiviral cytokines/chemokines. Beside the engagement of FcγRIIIa or CD16 by the Fc portion of anti-Env IgG1 and IgG3 Abs, natural killer (NK) cells are also able to directly kill infected cells and produce cytokines/chemokines in an Ab-independent manner. Responsiveness of NK cells depends on the integration of activating and inhibitory signals through NK receptors, which is determined by a process during their development known as education. NK cell education requires the engagement of inhibitory NK receptors by their human leukocyte antigen ligands to establish tolerance to self while allowing NK cells to respond to self cells altered by virus infection, transformation, stress, and to allogeneic cells. Here, we review recent findings regarding the impact of inter-individual differences in NK cell education on Ab-dependent functions such as ADCC and ADNKA, including what is known about the HIV Env epitope specificity of ADCC competent Abs and the conformation of HIV Env on target cells used for ADCC assays.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01033/fullnatural killer cellsantibody-dependent cellular cytotoxicityantibody-dependent natural killer cell activationnatural killer cell educationCD16inhibitory natural killer cell receptors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicole F. Bernard Nicole F. Bernard Nicole F. Bernard Nicole F. Bernard Zahra Kiani Zahra Kiani Alexandra Tremblay-McLean Alexandra Tremblay-McLean Sanket A. Kant Sanket A. Kant Christopher E. Leeks Christopher E. Leeks Franck P. Dupuy |
spellingShingle |
Nicole F. Bernard Nicole F. Bernard Nicole F. Bernard Nicole F. Bernard Zahra Kiani Zahra Kiani Alexandra Tremblay-McLean Alexandra Tremblay-McLean Sanket A. Kant Sanket A. Kant Christopher E. Leeks Christopher E. Leeks Franck P. Dupuy Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular Cytotoxicity Frontiers in Immunology natural killer cells antibody-dependent cellular cytotoxicity antibody-dependent natural killer cell activation natural killer cell education CD16 inhibitory natural killer cell receptors |
author_facet |
Nicole F. Bernard Nicole F. Bernard Nicole F. Bernard Nicole F. Bernard Zahra Kiani Zahra Kiani Alexandra Tremblay-McLean Alexandra Tremblay-McLean Sanket A. Kant Sanket A. Kant Christopher E. Leeks Christopher E. Leeks Franck P. Dupuy |
author_sort |
Nicole F. Bernard |
title |
Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular Cytotoxicity |
title_short |
Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular Cytotoxicity |
title_full |
Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular Cytotoxicity |
title_fullStr |
Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular Cytotoxicity |
title_full_unstemmed |
Natural Killer (NK) Cell Education Differentially Influences HIV Antibody-Dependent NK Cell Activation and Antibody-Dependent Cellular Cytotoxicity |
title_sort |
natural killer (nk) cell education differentially influences hiv antibody-dependent nk cell activation and antibody-dependent cellular cytotoxicity |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-08-01 |
description |
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present. Systems serology analyses implicated a broader range of Ab-dependent functions in protection from HIV infection, including but not limited to ADCC and Ab-dependent NK cell activation (ADNKA) for secretion of IFN-γ and CCL4 and expression of the degranulation marker CD107a. The existence of such correlations in the absence of bNAbs in the RV144 trial suggest that NK cells could be instrumental in protecting against HIV infection by limiting viral spread through Fc-mediated functions such as ADCC and the production of antiviral cytokines/chemokines. Beside the engagement of FcγRIIIa or CD16 by the Fc portion of anti-Env IgG1 and IgG3 Abs, natural killer (NK) cells are also able to directly kill infected cells and produce cytokines/chemokines in an Ab-independent manner. Responsiveness of NK cells depends on the integration of activating and inhibitory signals through NK receptors, which is determined by a process during their development known as education. NK cell education requires the engagement of inhibitory NK receptors by their human leukocyte antigen ligands to establish tolerance to self while allowing NK cells to respond to self cells altered by virus infection, transformation, stress, and to allogeneic cells. Here, we review recent findings regarding the impact of inter-individual differences in NK cell education on Ab-dependent functions such as ADCC and ADNKA, including what is known about the HIV Env epitope specificity of ADCC competent Abs and the conformation of HIV Env on target cells used for ADCC assays. |
topic |
natural killer cells antibody-dependent cellular cytotoxicity antibody-dependent natural killer cell activation natural killer cell education CD16 inhibitory natural killer cell receptors |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01033/full |
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