Recognition Of Ligands By Natural Killer Cells

自然杀伤细胞对配体的识别

• 批准号: 6521376
• 负责人: JOHN COLIGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6521376
• 关键词: CD antigens; MHC class I antigen; T cell receptor; antigen presentation; autoantigens; biological signal transduction; cytotoxic T lymphocyte; gene expression; human tissue; microarray technology; molecular shape; tissue /cell culture; transfection

CD28 functions as a cytotoxicity activation receptor in the natural killer (NK) cell line YT-Indy. To analyze the requirement of p56lck kinase in the function of killer inhibitory receptors, we transfected the p56lck negative YT-Indy cell line with the c143 gene encoding for KIR2DL2. Prevanadate treatment revealed KIR2DL2 phosphorylation in the YT-Indy-c143 cell line,as well as SHP1/SHP2 recruitment. YT-Indy-c143 cells were inhibited in their ability to lyse target cells expressing HLA-Cw3, a ligand for KIR2DL2. This inhibition was blocked by anti-KIR2DL2 or anti-HLA class I mAb. CD28 crosslinking on YT-Indy-c143 cells enhanced tyrosine phosphorylation of PLC-gamma 1. The simultaneous ligation of KIR2DL2 with mAb resulted in a decrease in CD28-induced tyrosine phosphorylation of PLC-gamma 1 confirming that dephosphorylation of this protein is involved in the KIR2DL2 induced inhibition of CD28-mediated cytotoxicity. As YT-Indy-c143 cells do not express detectable levels of p56lck, these results indicate that this kinase is not required for transmitting the negative signals generated by KIR2DL2 ligation.

CD28在天然杀伤（NK）细胞系yt-Indy中充当细胞毒性激活受体。为了分析p56LCK激酶在杀手抑制受体功能中的需求，我们用编码KIR2DL2的C143基因转染了p56LCK阴性YT-INDY细胞系。 Prevanate治疗显示YT-INDY-C143细胞系中的Kir2DL2磷酸化以及SHP1/SHP2募集。 YT-Indy-C143细胞的抑制能力裂解表达HLA-CW3的靶细胞，这是KiR2DL2的配体。这种抑制作用被抗KIR2DL2或抗HLA I类MAB阻塞。 CD28在YT-INDY-C143细胞上交联的CD28增强了PLC-gamma 1的酪氨酸磷酸化1。KiR2DL2与MAB的同时连接导致CD28诱导的PLC-GAMMA酪氨酸磷酸化降低了PLC-GAMMA 1确认该Protived cd2 rypiratied cd2 protived cd22 rypiription cd22 rypiriend cd22 cd rypiription cd2 rypiriend cd2 ripied cd ryprigied cd2 rigied cdy2 rigied cdy22细胞毒性。由于YT-Indy-C143细胞未表达可检测到的p56LCK水平，因此这些结果表明，该激酶不需要传输由KIR2DL2连接产生的负信号。