Role of HLA-G in innate immunity through direct activation of NF-kappa B in natural killer cells

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-kappa B 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 I kappa B alpha leading to nuclear translocation of NF-kappa B. 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-kappa B pathway in NK, cells. (c) 2007 Elsevier Ltd. All rights reserved.