Our aim is to understand how the complex system of interacting maternal KIR receptors and fetal HLA-C ligands affect trophoblast behaviour during placentation. Both KIR and HLA-C are polymorphic and genetic studies show that NK cells respond inadequately in certain maternal KIR/HLA-C combinations. KIR/HLA-C interactions are predicted to have particular biological importance during placentation because of high expression levels of KIR on uNK cells and HLA-C on trophoblast. We will study functional responses of primary uterine NK cells in women with known KIR genotypes using in vitro assays that mimic different maternal KIR/fetal HLA-C combinations. A particular focus will be on KIR2DS1, the activating KIR for HLA-C2 group alleles, because women with a C2+ fetus are at particular risk of pre-eclampsia if they lack the KIR2DS1 gene. Using functional read-outs - including CD107 assays, cytokine production and microarrays, we will determine the uterus NK repertoire, expression and functional characters of different subpopulations from different fetus/mother HLA-C combinations; analyse how KIR2DS1+ or KIR2DS1- uNK subsets respond to targets expressing C1 or C2 and to primary trophoblast cells whose HLA-C status is known. These studies will lead to an understanding of how uNK cells regulate trophoblast invasion during placentation in normal and abnormal pregnancies.
I am a member of Prof Ashley Moffett’s group.
Funding: Wellcome Trust
- Maternal KIR and fetal HLA-C: a fine balance. Olympe Chazara, Shiqiu Xiong, and Ashley Moffett. J. Leukoc. Biol. 90: 000–000; 2011. (in proof)
- Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. Shiqiu Xiong, Karsten Köhler, Joanna Brzostek, et al. PLOS one. 12(5), 2010.
- IL-12 promotes HBV-specific central memory CD8+ T cell responses by PBMCs from chronic hepatitis B virus carriers. Shiqiu xiong, bingliang lin, xiang gao, et al. International immunopharmacology. 2007, 7(5), 578.