MHC CLASS-I ALLOANTIGEN SPECIFICITY OF LY-49+ IL-2-ACTIVATED NATURAL-KILLER-CELLS
MHC CLASS-I ALLOANTIGEN SPECIFICITY OF LY-49+ IL-2-ACTIVATED NATURAL-KILLER-CELLS
复制标题
DOI：
10.1038/358066a0
复制
发表时间：
1992-07-02
期刊：
影响因子：
64.8
通讯作者：
YOKOYAMA, WM
中科院分区：
文献类型：
--
作者：
KARLHOFER, FM;RIBAUDO, RK;YOKOYAMA, WM
尽管 NK 细胞能够裂解特定的肿瘤细胞 1,2，但 CD3- 自然杀伤 (NK) 细胞识别靶细胞的分子基础仍知之甚少。一般来说，靶细胞主要组织相容性复合体 (MHC) I 类抗原表达与 NK 细胞介导的裂解抗性相关 3-9，可能是因为 NK 细胞表面分子与 MHC I 类抗原结合，从而传递抑制信号 3,4。自然杀伤细胞同种异体特异性涉及 MHC I 类肽结合裂口 10，对这种同种异体特异性的进一步了解应该有助于深入了解 NK 细胞识别的分子机制。 C57BL/6 小鼠 (H-2b) 中 20% 的 CD3-NK 细胞 11 表达 Ly-49 细胞表面分子。在这里，我们表明，尽管 Ly-49 效应细胞能有效自发裂解，但表达 Ly-49 的 C57BL/6 衍生、白细胞介素 2 激活的 NK 细胞不会裂解展示 H-2d 或 H-2k 的靶细胞。这种优先抗性与靶细胞 MHC I 类抗原的表达相关。 H-2D(d)（而非 H-2K(d) 或 H-2L(d)）的转染和表达使易感靶标 (H-2b) 对 Ly-49+ 效应细胞产生抗性。针对 Ly-49 或 H-2D(d) 的 α-1/α-2 结构域的单克隆抗体消除了转染的抗性，表明 Ly-49 与 MHC I 类同种抗原 H-2D(d) 的肽结合结构域特异性相互作用，因为 Ly49+ 效应细胞不能被刺激裂解 H-2D(d) 靶标，我们的结果表明 NK 细胞可能具有抑制性受体，特异性识别 MHC I 类抗原。
THE molecular basis of target cell recognition by CD3- natural killer (NK) cells is poorly understood, despite the ability of NK cells to lyse specific tumour cells 1,2. In general, target cell major histocompatibility complex (MHC) class I antigen expression correlates with resistance to NK cell-mediated lysis 3-9, possibly because NK cell-surface molecules engage MHC class I antigens and consequently deliver inhibitory signals 3,4. Natural killer cell allospecificity involves the MHC class I peptide-binding cleft 10, and further understanding of this allospecificity should provide insight into the molecular mechanisms of NK cell recognition. The Ly-49 cell surface molecule is expressed by 20% of CD3- NK cells 11 in C57BL/6 mice (H-2b). Here we show that C57BL/6-derived, interleukin-2-activated NK cells expressing Ly-49 do not lyse target cells displaying H-2d or H-2k despite efficient spontaneous lysis by Ly-49- effector cells. This preferential resistance correlates with expression of target cell MHC class I antigens. Transfection and expression of H-2D(d), but not H-2K(d) or H-2L(d), renders a susceptible target (H-2b) resistant to Ly-49+ effector cells. The transfected resistance is abrogated by monoclonal antibodies directed against Ly-49 or the alpha-1/alpha-2 domains of H-2D(d), suggesting that Ly-49 specifically interacts with the peptide-binding domains of the MHC class I alloantigen, H-2D(d) Inas-much as Ly49+ effector cells cannot be stimulated to lyse H-2D(d) targets, our results indicate that NK cells may possess inhibitory receptors that specifically recognize MHC class I antigens.