Binstadt B A, Brumbaugh K M, Leibson P J
Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Immunol Rev. 1997 Feb;155:197-203. doi: 10.1111/j.1600-065x.1997.tb00952.x.
Cells may be protected from natural killer (NK)-cell-mediated killing by the expression of specific MHC class I complexes. This protective effect is due to the expression on NK cells of MHC class I-recognizing receptors which, upon ligation, transduce potent inhibitory signals into the NK cells. The molecular signalling mechanisms employed by the human NK-cell MHC-recognizing killer cell inhibitory receptors (KIR) and CD94 are the focus of this review. A sequential model of KIR signalling involving lck-dependent tyrosine phosphorylation of KIR and subsequent association of KIR with the SH2-containing tyrosine phosphatase, SHP-1, is presented. We explore how engagement of either KIR or CD94 modulates the protein tyrosine kinase-dependent biochemical signals responsible for activation of NK-cell cytotoxic function. Additionally, we discuss models of inhibitory signalling proposed for each of the lymphocyte lineages, emphasizing that disparate molecular mechanisms may be utilized by cells to produce similar biological responses.
细胞可通过特定MHC I类复合物的表达来免受自然杀伤（NK）细胞介导的杀伤作用。这种保护作用归因于NK细胞上MHC I类识别受体的表达，这些受体在连接后会向NK细胞转导强大的抑制信号。人类NK细胞MHC识别杀伤细胞抑制受体（KIR）和CD94所采用的分子信号传导机制是本综述的重点。本文提出了一种KIR信号传导的顺序模型，该模型涉及KIR的lck依赖性酪氨酸磷酸化以及随后KIR与含SH2的酪氨酸磷酸酶SHP-1的结合。我们探讨了KIR或CD94的参与如何调节负责激活NK细胞细胞毒性功能的蛋白酪氨酸激酶依赖性生化信号。此外，我们讨论了为每个淋巴细胞谱系提出的抑制性信号传导模型，强调细胞可能利用不同的分子机制来产生相似的生物学反应。
