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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02730


  • 1Harvard University, United States
  • 2University of Copenhagen, Denmark
  • 3Beth Israel Deaconess Medical Center, Harvard Medical School, United States
  • 4Cincinnati Children's Hospital Medical Center, United States

To establish a healthy pregnancy, maternal immune cells must tolerate fetal allo-antigens and remain competent to respond to infections both systemically and in placental tissues. Extravillous trophoblasts (EVT) are the most invasive cells of extra-embryonic origin to invade uterine tissues and express polymorphic Human Leucocyte Antigen-C (HLA-C) of both maternal and paternal origin. Thus, HLA-C is a 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. HLA-C is also the only classical MHC molecule expressed by EVT that can present a wide variety of peptides to maternal memory T cells and establish protective immunity. The expression of paternal HLA-C by EVT provides a target for maternal NK and T cells, whereas HLA-C expression levels may influence how this response is shaped. This dual function of HLA-C requires tight transcriptional regulation of its expression to balance induction of tolerance and immunity. Here, we critically review new insights into: i) the mechanisms controlling expression of HLA-C by EVT, ii) the mechanisms by which decidual NK cells, effector T cells and regulatory T cells recognize HLA-C allo-antigens, and iii) immune recognition of pathogen derived antigens in context of HLA-C.

Keywords: Regulatory T (Treg) cell, HLA-G, Decidual NK cells, trophoblast, Placenta, Pregnancy, human, Decidua, effector T cell, KIR

Received: 01 Oct 2019; Accepted: 07 Nov 2019.

Copyright: © 2019 Papúchová, Meissner, Li, Strominger and Tilburgs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Tamara Tilburgs, Harvard University, Cambridge, MA 02138, Massachusetts, United States,