Immunity at maternal–fetal interface: KIR/HLA (Allo)recognition*

Both KIR and HLA are the most variable gene families in the human genome. The recognition of the semi-allogeneic embryo-derived trophoblasts by maternal decidual NK (dNK) cells is essential for the establishment of the functional placenta. This recognition is based on the KIR-HLA interactions and trophoblast expresses a specific HLA profile that constitutes classical polymorphic HLA-C and non-classical oligomorphic HLA-E, HLA-F, and HLA-G molecules. This review highlights some features of the KIR/HLA-C (allo)recognition by decidual NK (dNK) cells as a main immune cell population specifically enriched at maternal-fetal interface during human early pregnancy. How KIR/HLA-C axis operates in pregnancy disorders and in the context of transplacental infections is discussed as well. We summarized old and new data on dNK-cell functional plasticity, their selective expression of KIR and fetal maternal/paternal HLA-C haplotypes present. Results showed that KIR-HLA-C combinations and the corresponding axis operate differently in each pregnancy, determined by the variability of both maternal KIR haplotypes and fetus' maternal/paternal HLA-C allotype combinations. Moreover, the maturation of NK cells strongly depends on if or not HLA allotypes for certain KIR are present. We suggest that the unique KIR/HLA combinations reached in each pregnancy (normal and pathological) should be studied according to well-defined guidelines and unified methodologies to have comparable results ease to interpret and use in clinics.