Ward Jeffrey P, Bonaparte Matthew I, Barker Edward
Department of Microbiology and Immunology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.
AIDS. 2004 Sep 3;18(13):1769-79. doi: 10.1097/00002030-200409030-00005.
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.
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.
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.
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.
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.
确定人类免疫缺陷病毒（HIV）感染细胞上人类白细胞抗原C（HLA-C）和人类白细胞抗原E（HLA-E）的存在是否会调节来自HIV感染细胞的自身自然杀伤（NK）细胞实施抗体依赖性细胞介导的细胞毒性（ADCC）。
通过阻断NK细胞上的抑制性受体与感染细胞上的I类主要组织相容性复合体（MHC）分子之间的相互作用，确定HLA-C和HLA-E控制NK细胞对包被抗gp120单克隆抗体的HIV感染自身T细胞杀伤的能力。
用植物血凝素处理的CD4 T细胞在体外感染HIV-1。通过去除CD4 T细胞将感染细胞与未感染细胞分离。感染细胞用51铬标记，用四种不同的抗HIV gp120单克隆抗体混合物处理，并与新鲜分离的自身NK细胞共培养，自身NK细胞在有或没有抗CD159a、抗CD158a和CD158b或三种抗体组合的情况下孵育。在4小时的细胞毒性试验中评估NK细胞对HIV感染细胞的杀伤作用。
当NK细胞抑制性受体（即CD158a、CD158b和CD159a）与HIV感染的自身T细胞上的I类MHC分子（即HLA-C和HLA-E）之间的相互作用被阻断时，观察到NK细胞对包被抗gp120的HIV感染细胞的杀伤作用急剧增加。
这些研究表明，HIV感染细胞上HLA-C和HLA-E分子的存在可能有助于逃避NK介导的对包被抗体的HIV感染细胞的杀伤。
