The role of soluble factors affecting the major histocompatibility complex class I molecules In an IN VITRO model of the fetomaternal interface

Human main histocompatibility complex is encoded in the short arm of chromosome 6 and can be divided into three main regions based on the proteins that it encodes. We have class I, class III and class II. Class I encodes for proteins that are expressed on the cell surface of almost all somatic cells and is related to the presentation of self-antigens. Class I can be sub-divided into two groups known as classical class I (Ia) and non-classical class I (Ib), and expressed on the cell surface as human leukocyte antigen (HLA). HLA-G is one of the members of HLA-Ib and, together with HLA-E and HLA-F, is thought to play a key role in maternal tolerance to the semi-allogenic embryo, one haplotype comes from the mother, and is shared with her, while the other comes from the father. At the trophoblast stage, embryos do not express HLA-II and only express HLA-C (Ia member). Based on these facts, important questions about the role of these antigens during pregnancy have arisen. Our premise is that PreImplantation Factor (PIF), a 15 amino acid peptide secreted only by viable embryos, seems to plays a key role in this regulation. In this study we have used the JEG-3 cell line as a human trophoblastic model to study the effect of PIF on HLA-I expression. JEG-3 cells were incubated at different concentrations and time points of PIF. Using a wide variety of techniques, we could detect that PIF significantly induced HLA-I expression, mainly HLA-G and -E, increased their invasion, proliferation in vitro. Also, PIF modified protein profile, detected by 2D electrophoresis. Compared with the untreated cells, 14 proteins were over-expressed and 8 were under-expressed. Our study suggests that PIF, has a regulatory effect on HLA-I in this cellular model and the fact that not only HLA-G was over-expressed can suggest new regulations pathways under the control of HLA-E.