Guillard Christine, Zidi Inès, Marcou Céline, Menier Catherine, Carosella Edgardo D, Moreau Philippe
Commissariat à l'Energie Atomique, Service de Recherches en Hémato-Immunologie, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.
Mol Immunol. 2008 Jan;45(2):419-27. doi: 10.1016/j.molimm.2007.06.160. Epub 2007 Aug 1.
HLA-G is a non-classical HLA class I molecule involved in immunotolerance. HLA-G protects the fetus from maternal immune recognition and promotes allograft acceptance and tumor escape. Its low polymorphism and primary function, which is not peptide presentation to T lymphocytes, led us to compare the signal transduced after interaction between HLA-G and its receptor to those of innate immunity receptors with their ligands. We investigated the role of HLA-G in the classical NF-kappaB pathway in natural killer (NK) cells, which is the major pathway activated by innate immunity receptors. In NK cells stimulated with HLA-G1-expressed cells, we demonstrate that HLA-G induces the phosphorylation and the degradation of IkappaBalpha leading to nuclear translocation of NF-kappaB. This effect is independent of the presence of ILT-2 receptors and is still observed using a peptide corresponding to the alpha-1 domain of HLA-G. All these data support an unsuspected role for HLA-G in innate immunity by activating classical NF-kappaB pathway in NK cells.
HLA - G是一种参与免疫耐受的非经典HLA I类分子。HLA - G可保护胎儿免受母体免疫识别，并促进同种异体移植的接受和肿瘤逃逸。其低多态性以及不向T淋巴细胞呈递肽段的主要功能，促使我们将HLA - G与其受体相互作用后转导的信号，与天然免疫受体与其配体相互作用后转导的信号进行比较。我们研究了HLA - G在自然杀伤（NK）细胞经典核因子κB（NF - κB）信号通路中的作用，该通路是天然免疫受体激活的主要信号通路。在用表达HLA - G1的细胞刺激NK细胞时，我们证明HLA - G可诱导IkappaBalpha的磷酸化和降解，导致NF - κB的核转位。这种效应不依赖于免疫球蛋白样转录物2（ILT - 2）受体的存在，并且使用与HLA - G的α - 1结构域对应的肽段时仍可观察到这种效应。所有这些数据支持HLA - G通过激活NK细胞中的经典NF - κB信号通路在天然免疫中发挥意想不到的作用。
