Detection of transcripts for a soluble form of the RT1-E MHC class Ib molecule in rat placenta

During pregnancy, the fetally derived placenta plays a critical role in establishing maternal immunological tolerance toward the developing fetus. To prevent a potentially harmful maternal immune response directed against the paternal antigens inherited by the fetus, the latter has developed a number of particularly efficient molecular regulatory mechanisms. In humans, the absence of expression of the polymorphic HLA-A and HLA-B class I molecules on trophoblast cells that are in contact with maternal tissue is compensated by the presence of HLA-C and the oligomorphic class Ib HLA-G and HLA-E. HLA-G is expressed both as soluble and membrane-bound forms, particularly by cells of the invading extravillous cytotrophoblast that are directly in contact with maternal decidual natural killer (NK) cells. Three types of function have been described for HLA-G, depending on the ligand with which it interacts. (1) HLA-G has the capacity to present nonamer peptides to the T-cell receptor of CD8 super(+) cytotoxic T cells. (2) HLA-G modulates maternal innate immunity by two dictinct mechanisms. First, it interacts with some killer cell immunoglobulin (Ig)-like receptors (KIR) and Ig-like transcripts (ILT) expressed on decidual NK cells and macrophages. Second, the leader peptide from HLA-G binds to HLA-E with high affinity and thereby allows expression of the latter at the cell surface, where it can subsequently interact with CD94/NKG2 heterodimers expressed by NK cells and subsets of T cells. (3) Finally, soluble HLA-G can induce apoptosis of activated CD8 super(+) cells by interacting with CD8 ligand.