Gumá Mónica, Busch Lisa K, Salazar-Fontana Laura I, Bellosillo Beatriz, Morte Carles, García Pilar, López-Botet Miguel
Molecular Immunopathology Unit, Universitat Pompeu Fabra (DCEXS), Barcelona, Spain.
Eur J Immunol. 2005 Jul;35(7):2071-80. doi: 10.1002/eji.200425843.
The CD94/NKG2C killer lectin-like receptor (KLR) specific for HLA-E is coupled to the KARAP/DAP12 adapter in a subset of NK cells, triggering their effector functions. We have studied the distribution and function of this KLR in T lymphocytes. Like other NK cell receptors (NKR), CD94/NKG2C was predominantly expressed by a CD8(+) T cell subset, though TCRgammadelta(+) NKG2C(+) and rare CD4(+) NKG2C(+) cells were also detected in some individuals. Coculture with the 721.221 HLA class I-deficient lymphoma cell line transfected with HLA-E (.221-AEH) induced IL-2Ralpha expression in CD94/NKG2C+ NK cells and a minor subset of CD94/NKG2C(+) T cells, promoting their proliferation; moreover, a similar response was triggered upon selective engagement of CD94/NKG2C with a specific mAb. CD8(+) TCRalphabeta CD94/NKG2C(+) T cell clones, that displayed different combinations of KIR and CD85j receptors, expressed KARAP/DAP12 which was co-precipitated by an anti-CD94 mAb. Specific engagement of the KLR triggered cytotoxicity and cytokine production in CD94/NKG2C(+) T cell clones, inducing as well IL-2Ralpha expression and a proliferative response. Altogether these results support that CD94/NKG2C may constitute an alternative T cell activation pathway capable of driving the expansion and triggering the effector functions of a CTL subset.
针对HLA - E的CD94/NKG2C杀伤性凝集素样受体（KLR）在一部分自然杀伤细胞（NK细胞）中与接头蛋白KARAP/DAP12偶联，触发其效应功能。我们研究了这种KLR在T淋巴细胞中的分布和功能。与其他NK细胞受体（NKR）一样，CD94/NKG2C主要由CD8(+) T细胞亚群表达，不过在一些个体中也检测到TCRγδ(+) NKG2C(+)和罕见的CD4(+) NKG2C(+)细胞。与转染了HLA - E的721.221 HLA I类缺陷淋巴瘤细胞系（.221 - AEH）共培养，可诱导CD94/NKG2C+ NK细胞和一小部分CD94/NKG2C(+) T细胞表达IL - 2Rα，促进其增殖；此外，用特异性单克隆抗体选择性结合CD94/NKG2C也能触发类似反应。显示不同KIR和CD85j受体组合的CD8(+) TCRαβ CD94/NKG2C(+) T细胞克隆表达KARAP/DAP12，其可被抗CD94单克隆抗体共沉淀。KLR与特异性配体结合可触发CD94/NKG2C(+) T细胞克隆的细胞毒性和细胞因子产生，同时也诱导IL - 2Rα表达和增殖反应。总之，这些结果支持CD94/NKG2C可能构成一种替代性T细胞活化途径，能够驱动一个细胞毒性T淋巴细胞（CTL）亚群的扩增并触发其效应功能。
