Role of HLA-G in innate immunity through direct activation of NF-kappaB 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-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.
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.
Christine
C
Guillard
Inès
I
Zidi
Céline
C
Marcou
Catherine
C
Menier
Edgardo D
ED
Carosella
Philippe
P
Moreau
D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000235:genetics; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D000072000:NF-KappaB Inhibitor alpha; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000276:immunology*
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D010455:Peptides; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11