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AIDS. 2004 Sep 3;18(13):1769-79.

HLA-C and HLA-E reduce antibody-dependent natural killer cell-mediated cytotoxicity of HIV-infected primary T cell blasts.

Author information

  • 1Department of Microbiology and Immunology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.

Abstract

OBJECTIVE:

To determine whether the presence of HLA-C and HLA-E on HIV-infected cells modulates autologous natural killer (NK) cells from implementing antibody-dependent cell-mediated cytotoxicity (ADCC) of HIV-infected cells.

DESIGN:

The capability of HLA-C and HLA-E to control NK cell killing of HIV-infected autologous T cells coated with anti-gp120 monoclonal antibody was determined by blocking the interaction between the inhibitory receptors on NK cells and the MHC class I molecules on infected cells.

METHODS:

Phytohemagglutinin-treated CD4 T cells were infected in vitro with HIV-1. Infected cells were separated from uninfected cells by removal of CD4 T cells. Infected cells were labeled with chromium-51, treated with a cocktail of four different monoclonal antibodies against HIV gp120, and co-cultured with freshly isolated autologous NK cells that were incubated with or without anti-CD159a, anti-CD158a, and CD158b, or all three antibodies combined. Killing of the HIV-infected cells by NK cells was assessed in a 4 h cytotoxic assay.

RESULTS:

When the interaction between NK cell inhibitory receptors (i.e., CD158a, CD158b, and CD159a) and MHC class I molecules (i.e., HLA-C and HLA-E) on HIV-infected autologous T cells was blocked, a drastic increase in killing of anti-gp120-coated HIV-infected cells by NK cells was observed.

CONCLUSION:

These studies indicate that the presence of HLA-C and HLA-E molecules on HIV-infected cells may facilitate evasion of NK-mediated killing of antibody-coated HIV-infected cells.

PMID:
15316337
[PubMed - indexed for MEDLINE]
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