Robust NK cell-mediated human immunodeficiency virus (HIV)-specific antibody-dependent responses in HIV-infected subjects.
Antibody-dependent cellular cytotoxicity (ADCC) is a potentially effective adaptive immune response to human immunodeficiency virus (HIV) infection. The study of ADCC responses has been hampered by the lack of simple methods to quantify these responses and map effective epitopes. We serendipitously observed that standard intracellular cytokine assays on fresh whole blood from a cohort of 26 HIV-infected subjects identified non-T lymphocytes expressing gamma interferon (IFN-gamma) in response to overlapping linear peptides spanning HIV-1 proteins. The effector cells were CD3(-) CD4(-) CD8(-) CD14(-) CD2(+) CD56(+/-) NK lymphocytes and degranulated granzyme B and perforin in response to antigen stimulation. Serum transfer assays demonstrated that the specific response was mediated by immunoglobulin G. Fresh blood samples from half of the HIV-infected cohort demonstrated robust HIV peptide-specific IFN-gamma expression by NK cells, predominately to Env, Pol, and Vpu HIV-1 proteins. Responses were readily mapped to define minimal epitopes utilizing this assay. Antibody-dependent, HIV-specific NK cell recognition, involving components of both innate and adaptive immune systems, represents a potentially effective immune response to induce by vaccination.
Stratov
Ivan
I
Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
Chung
Amy
A
Kent
Stephen J
SJ
D000595:Amino Acid Sequence; D015415:Biomarkers; D017252:CD3 Complex / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D018604:Epitope Mapping; D053804:Granzymes / Q000378:metabolism; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D054298:Human Immunodeficiency Virus Proteins / Q000097:blood / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D008969:Molecular Sequence Data; D054353:Perforin / Q000494:pharmacology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D054334:Viral Regulatory and Accessory Proteins / Q000097:blood / Q000276:immunology; D000086082:Viroporin Proteins
D015415:Biomarkers; D017252:CD3 Complex; D019002:CD56 Antigen; D053804:Granzymes; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D007371:Interferon-gamma; D054353:Perforin; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins