Presentation and recognition of placental, fetal, and pathogen-derived antigens in human pregnancy

Abstract To establish a healthy pregnancy, the maternal immune system must tolerate fetal and placental allo-antigens, yet remain competent to respond to infections. Thus, immune recognition and presentation of placental, fetal, and pathogen-derived antigens in the right context is essential to establish maternal-fetal tolerance and immunity throughout pregnancy. Here, we review new insights into how maternal decidual immune cells at the maternal-fetal interface can recognize and respond to nonself antigens. A major focus is placed on HLA-C as the key molecule that can elicit allogeneic immune responses by maternal T and NK cells and for which maternal-fetal immune tolerance needs to be established. In addition, HLA-C is also the only classical major histocompatibility molecule expressed by extravillous trophoblast that can present a wide variety of pathogen-derived peptides and activate maternal T and NK cells and is crucial in generation of a protective immune responses to intracellular pathogens.