TY - JOUR
T1 - HLA-C and HLA-E reduce antibody-dependent natural killer cell-mediated cytotoxicity of HIV-infected primary T cell blasts
AU - Ward, Jeffrey P.
AU - Bonaparte, Matthew I.
AU - Barker, Edward
PY - 2004/9/3
Y1 - 2004/9/3
N2 - 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.
AB - 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.
KW - AIDS
KW - Antibodies
KW - Cytotoxicity
KW - Fc receptor
KW - Human
KW - MHC
KW - Natural killer cells
KW - Viral
UR - http://www.scopus.com/inward/record.url?scp=4444276508&partnerID=8YFLogxK
U2 - 10.1097/00002030-200409030-00005
DO - 10.1097/00002030-200409030-00005
M3 - Article
C2 - 15316337
AN - SCOPUS:4444276508
VL - 18
SP - 1769
EP - 1779
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 13
ER -