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Journal of Virology, June 2008, p. 5450-5459, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.01952-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Robust NK Cell-Mediated Human Immunodeficiency Virus (HIV)-Specific Antibody-Dependent Responses in HIV-Infected Subjects{triangledown}

Ivan Stratov,1,2,3,4 Amy Chung,1 and Stephen J. Kent1,2,3*

Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia,1 Melbourne Sexual Health Clinic, Carlton, Victoria 3053, Australia,2 Infectious Diseases Unit, Alfred Hospital, Prahran 3181, Australia,3 Burnet Institute, Commercial Road, Prahran 3181, Australia4

Received 5 September 2007/ Accepted 22 February 2008

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. Phone: 61 383449939. Fax: 61 383443846. E-mail: skent{at}unimelb.edu.au

{triangledown} Published ahead of print on 19 March 2008.

Journal of Virology, June 2008, p. 5450-5459, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.01952-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tiemessen, C. T., Shalekoff, S., Meddows-Taylor, S., Schramm, D. B., Papathanasopoulos, M. A., Gray, G. E., Sherman, G. G., Coovadia, A. H., Kuhn, L. (2009). Cutting Edge: Unusual NK Cell Responses to HIV-1 Peptides Are Associated with Protection against Maternal-Infant Transmission of HIV-1. J. Immunol. 182: 5914-5918 [Abstract] [Full Text]  
  • Chung, A. W., Rollman, E., Center, R. J., Kent, S. J., Stratov, I. (2009). Rapid Degranulation of NK Cells following Activation by HIV-Specific Antibodies. J. Immunol. 182: 1202-1210 [Abstract] [Full Text]  


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