HLA-G: At the Interface of Maternal–Fetal Tolerance

Trends in Immunology

Volumn 38, Issue 4, 2017, Pages 272-286

  Ferreira, Leonardo M R ^a,b   Meissner, Torsten B ^a   Tilburgs, Tamara ^a   Strominger, Jack L ^a  

^a Harvard University   (United States)

^b HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HLA G ANTIGEN; ALLOANTIGEN;

ANTIGEN EXPRESSION; ANTIGEN FUNCTION; CELL FUNCTION; CELL INTERACTION; DECIDUA; DECIDUAL NATURAL KILLER CELL; FEMALE; FETUS; GENE EXPRESSION REGULATION; GENETIC DISTANCE; GENETIC TRANSCRIPTION; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; MATERNAL FETAL TOLERANCE; NATURAL KILLER CELL; NONHUMAN; PLACENTA; PREGNANCY; PROTEIN INTERACTION; REVIEW; TRANSCRIPTION REGULATION; TROPHOBLAST; ANIMAL; HISTOCOMPATIBILITY; IMMUNOLOGY; METABOLISM; MOTHER FETUS RELATIONSHIP; TRANSPLANTATION TOLERANCE;

ANIMALS; FEMALE; HISTOCOMPATIBILITY; HLA-G ANTIGENS; HUMANS; ISOANTIGENS; MATERNAL-FETAL RELATIONS; PREGNANCY; TRANSPLANTATION TOLERANCE; TROPHOBLASTS;

EID: 85014448693     PISSN: 14714906     EISSN: 14714981     Source Type: Journal    
DOI: 10.1016/j.it.2017.01.009     Document Type: Review

References (119)

1. 1 Medawar, P.B., Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 44 (1953), 320–338.
2. 2 Suciu-Foca, N., et al. Anti-idiotypic antibodies to anti-HLA receptors induced by pregnancy. Proc. Natl. Acad. Sci. U. S. A. 80 (1983), 830–834.
3. 3 van Kampen, C.A., et al. Kinetics of the pregnancy-induced humoral and cellular immune response against the paternal HLA class I antigens of the child. Hum. Immunol. 63 (2002), 452–458.
4. 4 Tilburgs, T., et al. Fetal-maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells. J. Reprod. Immunol. 82 (2009), 148–157.
5. bright regulatory T cells from the peripheral blood to the decidua in human pregnancy. J. Immunol. 180 (2008), 5737–5745.
6. 6 Samstein, R.M., et al. Extrathymic generation of regulatory T cells in placental mammals mitigates maternal–fetal conflict. Cell 150 (2012), 29–38.
7. 7 Kopcow, H.D., et al. Human decidual NK cells form immature activating synapses and are not cytotoxic. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 15563–15568.
8. 8 Vince, G.S., et al. Flow cytometric characterisation of cell populations in human pregnancy decidua and isolation of decidual macrophages. J. Immunol. Methods 132 (1990), 181–189.
9. 9 Erlebacher, A., Immunology of the maternal–fetal interface. Annu. Rev. Immunol. 31 (2013), 387–411.
10. 10 Moffett-King, A., Natural killer cells and pregnancy. Nat. Rev. Immunol. 2 (2002), 656–663.
11. 11 Tilburgs, T., et al. The HLA-G cycle provides for both NK tolerance and immunity at the maternal–fetal interfac. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 13312–13317.
12. 12 Guerin, L., et al. CD1 antigen presentation and autoreactivity in the pregnant human uterus. Am. J. Reprod. Immunol. 74 (2015), 126–135.
13. 13 Houser, B.L., et al. Two unique human decidual macrophage populations. J. Immunol. 186 (2011), 2633–2642.
14. 14 Apps, R., et al. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies. Immunology 127 (2009), 26–39.
15. 15 Orr, H.T., et al. Use of HLA loss mutants to analyse the structure of the human major histocompatibility complex. Nature 296 (1982), 454–456.
16. 16 Kovats, S., et al. A class I antigen, HLA-G, expressed in human trophoblasts. Science 248 (1990), 220–223.
17. 17 Pazmany, L., et al. Protection from natural killer cell-mediated lysis by HLA-G expression on target cells. Science 274 (1996), 792–795.
18. 18 Rouas-Freiss, N., et al. The α1 domain of HLA-G1 and HLA-G2 inhibits cytotoxicity induced by natural killer cells: is HLA-G the public ligand for natural killer cell inhibitory receptors?. Proc. Natl. Acad. Sci. U. S. A. 94 (1997), 5249–5254.
19. 19 Yokoyama, W.M., The mother–child union: the case of missing-self and protection of the fetus. Proc. Natl. Acad. Sci. U. S. A. 94 (1997), 5998–6000.
20. 20 Rajagopalan, S., Long, E.O., A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J. Exp. Med. 189 (1999), 1093–1100.
21. 21 Redman, C.W., et al. Class 1 major histocompatibility complex antigens on human extra-villous trophoblast. Immunology 52 (1984), 457–468.
22. 22 Ellis, S.A., et al. Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology 59 (1986), 595–601.
23. 23 Geraghty, D.E., et al. A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment. Proc. Natl. Acad. Sci. U. S. A. 84 (1987), 9145–9149.
24. 24 Bodmer, J.G., et al. Nomenclature for factors of the HLA system, 1989. Immunol. Today 11 (1990), 3–10.
25. 25 Chumbley, G., et al. Resistance of HLA-G and HLA-A2 transfectants to lysis by decidual NK cells. Cell Immunol. 155 (1994), 312–322.
26. 26 Lee, N., et al. The membrane-bound and soluble forms of HLA-G bind identical sets of endogenous peptides but differ with respect to TAP association. Immunity 3 (1995), 591–600.
27. 27 Gobin, S.J., van den Elsen, P.J., Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G. Hum. Immunol. 61 (2000), 1102–1107.
28. 28 O'Brien, M., et al. Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLA-G gene in susceptibility to the disease. Cell Mol. Life Sci. 58 (2001), 1943–1949.
29. 29 Boyson, J.E., et al. Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc. Natl. Acad. Sci. U. S. A. 99 (2002), 16180–16185.
30. 30 Clements, C.S., et al. Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 3360–3365.
31. 31 Rajagopalan, S., et al. Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol., 4, 2006, e9.
32. 32 LeMaoult, J., et al. Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells. Blood 109 (2007), 2040–2048.
33. 33 Rajagopalan, S., Long, E.O., Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 20596–20601.
34. 34 Ferreira, L.M., et al. A distant trophoblast-specific enhancer controls HLA-G expression at the maternal–fetal interface. Proc. Natl. Acad. Sci. U. S. A. 113 (2016), 5364–5369.
35. 35 Yelavarthi, K.K., et al. Cellular distribution of HLA-G mRNA in transgenic mouse placentas. J. Immunol. 151 (1993), 3638–3645.
36. 36 Moreau, P., et al. HLA-G gene transcriptional regulation in trophoblasts and blood cells: differential binding of nuclear factors to a regulatory element located 1.1 kb from exon 1. Hum. Immunol. 52 (1997), 41–46.
37. 37 Flajollet, S., et al. RREB-1 is a transcriptional repressor of HLA-G. J. Immunol. 183 (2009), 6948–6959.
38. + extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes. Proc. Natl. Acad. Sci. U S A 112 (2015), 7219–7224.
39. 39 Solier, C., et al. HLA-G unique promoter region: functional implications. Immunogenetics 53 (2001), 617–625.
40. 40 Meissner, T.B., et al. NLR family member NLRC5 is a transcriptional regulator of MHC class I genes. Proc. Natl. Acad. Sci. U S A 107 (2010), 13794–13799.
41. 41 Gobin, S.J., et al. HLA-G transactivation by cAMP-response element-binding protein (CREB). An alternative transactivation pathway to the conserved major histocompatibility complex (MHC) class I regulatory routes. J. Biol. Chem. 277 (2002), 39525–39531.
42. 42 Ikeno, M., et al. LINE1 family member is negative regulator of HLA-G expression. Nucleic Acids Res. 40 (2012), 10742–10752.
43. 43 Majumder, P., et al. The human major histocompatibility complex class II HLA-DRB1 and HLA-DQA1 genes are separated by a CTCF-binding enhancer-blocking element. J. Biol. Chem. 281 (2006), 18435–18443.
44. 44 Majumder, P., et al. The insulator factor CTCF controls MHC class II gene expression and is required for the formation of long-distance chromatin interactions. J. Exp. Med. 205 (2008), 785–798.
45. 45 Yuhki, N., et al. Comparative genome organization of human, murine, and feline MHC class II region. Genome Res. 13 (2003), 1169–1179.
46. 46 Melnikov, A., et al. Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay. Nat. Biotechnol. 30 (2012), 271–277.
47. 47 Ma, G.T., et al. GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo. Development 124 (1997), 907–914.
48. 48 Begay, V., et al. Essential requirement of CCAAT/enhancer binding proteins in embryogenesis. Mol. Cell Biol. 24 (2004), 9744–9751.
49. 49 Harrison, G.A., et al. A 14 bp deletion polymorphism in the HLA-G gene. Hum. Mol. Genet., 2, 1993, 2200.
50. 50 Rousseau, P., et al. The 14 bp deletion-insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability. Hum. Immunol. 64 (2003), 1005–1010.
51. 51 Porto, I.O., et al. MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G. Mol. Immunol. 65 (2015), 230–241.
52. 52 Manaster, I., et al. MiRNA-mediated control of HLA-G expression and function. PLoS One, 7, 2012, e33395.
53. 53 Donker, R.B., et al. The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes. Mol. Hum. Reprod. 18 (2012), 417–424.
54. 54 Moreau, P., et al. Non-classical transcriptional regulation of HLA-G: an update. J. Cell Mol. Med. 13 (2009), 2973–2989.
55. 55 Quach, K., et al. A combination of single nucleotide polymorphisms in the 3′untranslated region of HLA-G is associated with pre-eclampsia. Hum. Immunol. 75 (2014), 1163–1170.
56. 56 Tan, Z., et al. Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am. J. Hum. Genet. 81 (2007), 829–834.
57. 57 Djurisic, S., Hviid, T.V., HLA class Ib molecules and immune cells in pregnancy and pre-eclampsia. Front. Immunol., 5, 2014, 652.
58. 58 de Albuquerque, R.S., et al. Association of HLA-G 3′ untranslated region variants with type 1 diabetes mellitus. Hum. Immunol. 77 (2016), 358–364.
59. 59 Golos, T.G., et al. On the role of placental major histocompatibility complex and decidual leukocytes in implantation and pregnancy success using non-human primate models. Int. J. Dev. Biol. 54 (2010), 431–443.
60. 60 Llano, M., et al. HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Eur. J. Immunol. 28 (1998), 2854–2863.
61. 61 Avril, T., et al. Trophoblast cell line resistance to NK lysis mainly involves an HLA class I-independent mechanism. J. Immunol. 162 (1999), 5902–5909.
62. 62 King, A., et al. HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. Eur. J. Immunol. 30 (2000), 1623–1631.
63. 63 Rouas-Freiss, N., et al. Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc. Natl. Acad. Sci. U S A 94 (1997), 11520–11525.
64. 64 Hanna, J., et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat. Med. 12 (2006), 1065–1074.
65. 65 Siewiera, J., et al. Human cytomegalovirus infection elicits new decidual natural killer cell effector functions. PLoS Pathog., 9, 2013, e1003257.
66. 66 Patel, D.M., et al. Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition. J. Immunol. 163 (1999), 5201–5210.
67. 67 Cone, R.E., et al. Antigen-binding specificity of isolated cell-surface immunoglobulin from thymus cells activated to histocompatibility antigens. Proc. Natl. Acad. Sci. U S A 69 (1972), 2556–2560.
68. 68 Martinez-Martin, N., T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis. Immunity 35 (2011), 208–222.
69. 69 Dopfer, E.P., et al. A new vampire saga: the molecular mechanism of T cell trogocytosis. Immunity 35 (2011), 151–153.
70. 70 Qureshi, O.S., et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332 (2011), 600–603.
71. + can be transferred via trogocytosis from myeloma cells to T cells and are associated with poor prognosis. Blood 120 (2012), 2055–2063.
72. 72 Rajagopalan, S., et al. DNA-PKcs controls an endosomal signaling pathway for a proinflammatory response by natural killer cells. Sci. Signal., 3, 2010, ra14.
73. 73 Koopman, L.A., et al. Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential. J. Exp. Med. 198 (2003), 1201–1212.
74. 74 HoWangYin, K.Y., et al. Proper regrafting of Ig-like transcript 2 after trogocytosis allows a functional cell–cell transfer of sensitivity. J. Immunol. 186 (2011), 2210–2218.
75. 75 Li, C., et al. HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells. Proc. Natl. Acad. Sci. U S A 106 (2009), 5767–5772.
76. + T-lymphocytes. J. Reprod. Immunol. 48 (2000), 17–26.
77. 77 Naji, A., et al. Binding of HLA-G to ITIM-bearing Ig-like transcript 2 receptor suppresses B cell responses. J. Immunol. 192 (2014), 1536–1546.
78. 78 Shiroishi, M., et al. Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc. Natl. Acad. Sci. U S A 100 (2003), 8856–8861.
79. 79 Caumartin, J., et al. Trogocytosis-based generation of suppressive NK cells. EMBO J. 26 (2007), 1423–1433.
80. 80 HoWangYin, K.Y., et al. Different functional outcomes of intercellular membrane transfers to monocytes and T cells. Cell Mol. Life Sci. 67 (2010), 1133–1145.
81. 81 Gonen-Gross, T., et al. Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J. Immunol. 171 (2003), 1343–1351.
82. 82 Apps, R., et al. A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1. Eur J. Immunol. 37 (2007), 1924–1937.
83. 83 Shiroishi, M., et al. Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J. Biol. Chem. 281 (2006), 10439–10447.
84. 84 Shiroishi, M., et al. Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d). Proc. Natl. Acad. Sci. U S A 103 (2006), 16412–16417.
85. 85 Gustafsson, C., et al. Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype. PLoS One, 3, 2008, e2078.
86. + T cells awakened by infections. J. Reprod. Immunol., 2016.
87. + effector-memory T cells with unique properties. J. Immunol. 185 (2010), 4470–4477.
88. 88 Le Gal, F.A., et al. HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes. Int. Immunol. 11 (1999), 1351–1356.
89. 89 Saverino, D., et al. The CD85/LIR-1/ILT2 inhibitory receptor is expressed by all human T lymphocytes and down-regulates their functions. J. Immunol. 165 (2000), 3742–3755.
90. 90 Paul, P., et al. HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance. Proc. Natl. Acad. Sci. U S A 95 (1998), 4510–4515.
91. 91 Horii, M., et al. Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease. Proc. Natl. Acad. Sci. U S A 113 (2016), E3882–E3891.
92. 92 Schlesinger, M., Uterus of rodents as site for manifestation of transplantation immunity against transplantable tumors. J. Natl. Cancer Inst. 28 (1962), 927–945.
93. 93 Simmons, R.L., Russell, P.S., The antigenicity of mouse trophoblast. Ann. N. Y. Acad. Sci. 99 (1962), 717–732.
94. 94 Balkundi, D.R., et al. Labor-associated changes in Fas ligand expression and function in human placenta. Pediatr. Res. 47 (2000), 301–308.
95. 95 Phillips, T.A., et al. TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege. J. Immunol. 162 (1999), 6053–6059.
96. 96 Honig, A., et al. Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno-fetal tolerance. J. Reprod. Immunol. 61 (2004), 79–86.
97. 97 Hunt, J.S., et al. Fas ligand is positioned in mouse uterus and placenta to prevent trafficking of activated leukocytes between the mother and the conceptus. J. Immunol. 158 (1997), 4122–4128.
98. 98 Munn, D.H., et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281 (1998), 1191–1193.
99. 99 Kudo, Y., et al. Decreased tryptophan catabolism by placental indoleamine 2,3-dioxygenase in pre-eclampsia. Am. J. Obstet. Gynecol. 188 (2003), 719–726.
100. 100 Holets, L.M., et al. Trophoblast CD274 (B7-H1) is differentially expressed across gestation: influence of oxygen concentration. Biol. Reprod. 74 (2006), 352–358.
101. 101 Guleria, I., Sayegh, M.H., Maternal acceptance of the fetus: true human tolerance. J. Immunol. 178 (2007), 3345–3351.
102. 102 Zhang, Y.H., et al. Recent insight into the role of the PD-1/PD-L1 pathway in feto-maternal tolerance and pregnancy. Am. J. Reprod. Immunol. 74 (2015), 201–208.
103. + regulatory T cells and foster T cell suppressive activity. Biol. Reprod. 94 (2016), 1–11.
104. 104 Du, M.R., et al. Embryonic trophoblasts induce decidual regulatory T cell differentiation and maternal–fetal tolerance through thymic stromal lymphopoietin instructing dendritic cells. J. Immunol. 192 (2014), 1502–1511.
105. 105 Apps, R., et al. Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells. Placenta 32 (2011), 33–43.
106. 106 Boyle, A.P., et al. High-resolution mapping and characterization of open chromatin across the genome. Cell 132 (2008), 311–322.
107. 107 Buenrostro, J.D., Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10 (2013), 1213–1218.
108. 108 Johnson, D.S., et al. Genome-wide mapping of in vivo protein-DNA interactions. Science 316 (2007), 1497–1502.
109. 109 de Wit, E., de Laat, W., A decade of 3C technologies: insights into nuclear organization. Genes Dev. 26 (2012), 11–24.
110. 110 Rajagopal, N., et al. High-throughput mapping of regulatory DNA. Nat. Biotechnol. 34 (2016), 167–174.
111. 111 Amiot, L., et al. HLA-G transcription studies during the different stages of normal and malignant hematopoiesis. Tissue Antigens 48 (1996), 609–614.
112. 112 Seitz, C., et al. The monoclonal antibody HCA2 recognises a broadly shared epitope on selected classical as well as several non-classical HLA class I molecules. Mol. Immunol. 35 (1998), 819–827.
113. 113 Zhao, L., et al. Reassessment of HLA-G isoform specificity of MEM-G/9 and 4H84 monoclonal antibodies. Tissue Antigens 80 (2012), 231–238.
114. 114 Real, L.M., et al. Expression of HLA G in human tumors is not a frequent event. Int. J. Cancer 81 (1999), 512–518.
115. 115 Frumento, G., et al. Melanomas and melanoma cell lines do not express HLA-G, and the expression cannot be induced by γIFN treatment. Tissue Antigens 56 (2000), 30–37.
116. 116 Paul, P., et al. Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies. Cancer Res. 59 (1999), 1954–1960.
117. 117 Morandi, F., et al. Recent advances in our understanding of HLA-G biology: lessons from a wide spectrum of human diseases. J. Immunol. Res., 2016, 2016, 4326495.
118. 118 de Kruijf, E.M., et al. HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J. Immunol. 185 (2010), 7452–7459.
119. 119 Li, X.J., et al. Human leukocyte antigen-G (HLA-G) expression in cervical cancer lesions is associated with disease progression. Hum. Immunol. 73 (2012), 946–949.