The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface
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 expr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02730/full |
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| author | Henrieta Papúchová Torsten B. Meissner Torsten B. Meissner Qin Li Jack L. Strominger Tamara Tilburgs Tamara Tilburgs |
| author_facet | Henrieta Papúchová Torsten B. Meissner Torsten B. Meissner Qin Li Jack L. Strominger Tamara Tilburgs Tamara Tilburgs |
| author_sort | Henrieta Papúchová |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T10:04:32Z |
| format | Article |
| id | doaj.art-4360c5f15d714c469ad24f29c97e1d3a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T10:04:32Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4360c5f15d714c469ad24f29c97e1d3a2022-12-21T19:44:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-12-011010.3389/fimmu.2019.02730502120The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal InterfaceHenrieta Papúchová0Torsten B. Meissner1Torsten B. Meissner2Qin Li3Jack L. Strominger4Tamara Tilburgs5Tamara Tilburgs6Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United StatesDepartment of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United StatesDivision of Immunobiology, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United StatesTo 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.02730/fullhumanpregnancydeciduaregulatory T cellseffector T cellsdecidual NK cells |
| spellingShingle | Henrieta Papúchová Torsten B. Meissner Torsten B. Meissner Qin Li Jack L. Strominger Tamara Tilburgs Tamara Tilburgs The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface Frontiers in Immunology human pregnancy decidua regulatory T cells effector T cells decidual NK cells |
| title | The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface |
| title_full | The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface |
| title_fullStr | The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface |
| title_full_unstemmed | The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface |
| title_short | The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface |
| title_sort | dual role of hla c in tolerance and immunity at the maternal fetal interface |
| topic | human pregnancy decidua regulatory T cells effector T cells decidual NK cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02730/full |
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