Inhibitory NK Receptor Recognition of HLA-G: Regulation by Contact Residues and by Cell Specific Expression at the Fetal-Maternal Interface

摘要: The non-classical HLA-G protein is distinguished from the classical MHC class I molecules by its expression pattern, low polymorphism and ability to form complexes on cell surface. special role of in maternal-fetal interface has been attributed interact with specific receptors found maternal immune cells. However this interaction restricted a limited number receptors. In study we elucidate reason for phenomenon comparing contact residues responsible MHC-KIR interactions. This alignment revealed marked difference between molecule other molecules. By mutating these equivalent residues, regained an interacting KIR inhibitory NK cells derived either peripheral blood or decidua. Functional killing assays further substantiated binding results. Furthermore, double immunofluorescent staining placental sections that while conformed was expressed all extravillous trophoblasts, free heavy chain more distal column, invasion front. Overall suggest evolved only some thus allowing control inhibition, permitting appropriate cytokine growth factor production necessary viable fetal interface.