The microstructure in the placenta is influenced by the functional diversity of HLA-G allelic variants

The main expression sites of HLA-G are human extravillous trophoblast cells. The interaction of HLA-G with uterine NK cells promotes their maturation and differentiation into decidual NK (dNK) cells. dNK cells secrete chemokines, cytokines, and proangiogenic factors in favor of a vascular remodeling and an immune suppressive microenvironment of the decidua. HLA-G is the most polymorphic member of the oligomorphic non-classical HLA molecule family; yet, the impact of polymorphic differences is not comprehensively understood. sHLA-G levels in embryo culture medium correlate with successful pregnancy; however, it remains questionable if HLA-G allelic diversity impacts on the outcome of dNK cell development. We utilized synthetic sHLA-G*01:01, 01:03, and 01:04 molecules and transduced K652/mHLA-G*01:01, 01:03, and 01:04 cells to study the biological interaction between HLA-G alleles and primary NK cells of human term placenta. Despite its low frequency, HLA-G*01:04 and not the most prevalent allele HLA-G*01:01 appear to be strong catalysts of dNK cell proliferation. Concluding, this study illustrates novel insights into the impact and binding efficiency of the three most common variants of HLA-G on primary placental NK cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00251-019-01121-0) contains supplementary material, which is available to authorized users.