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

Abstract 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.