Placenta
Volume 28 , Pages S57-S63 , April 2007

A Commentary on Gestational Programming and Functions of HLA-G in Pregnancy

  • J.S. Hunt

      Affiliations

    • Department of Anatomy and Cell Biology, University of Kansas Medical Center, Mail Stop 3038, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 913 588 7270; fax: +1 913 588 7180.
    • ,
  • P.J. Morales

      Affiliations

    • Department of Anatomy and Cell Biology, University of Kansas Medical Center, Mail Stop 3038, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
    • ,
  • J.L. Pace

      Affiliations

    • Department of Anatomy and Cell Biology, University of Kansas Medical Center, Mail Stop 3038, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
    • ,
  • A.T. Fazleabas

      Affiliations

    • Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL 60612-7313, USA
    • ,
  • D.K. Langat

      Affiliations

    • Department of Anatomy and Cell Biology, University of Kansas Medical Center, Mail Stop 3038, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA

,Accepted 3 January 2007.

References 

  1. Geraghty DE, Koller BH, Orr HT. A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment. Proc Natl Acad Sci USA. 1987;84:9145–9149
  2. Hunt JS, Orr HT. HLA and maternal-fetal recognition. FASEB J. 1992;6:2344–2348
  3. Le Bouteiller P, Mallet V. HLA-G and pregnancy. Rev Reprod. 1997;2:7–13
  4. Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB J. 2005;19:681–693
  5. Hunt JS, McIntire RH, Petroff MG. Immunobiology of human pregnancy. In:  Neill JD editors. 3rd ed.. Knobil and Neill's physiology of reproduction. Vol. 2:St. Louis, MO: Elsevier/Academic Press; 2006;p. 2759–2785
  6. Hunt JS. Stranger in a strange land. Immunol Rev. 2006;213:36–47
  7. Kovats S, Main EK, Librach C, Stubblebein M, Fisher SJ, DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990;248:220–223
  8. Ellis SA, Sargent IL, Redman CW, McMichael AJ. Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology. 1986;59:595–601
  9. Ellis SA, Palmer MS, McMichael AJ. Human trophoblast and the choriocarcinoma cell line BeWo express a truncated HLA class I molecule. J Immunol. 1990;144:731–735
  10. Mallet V, Blaschitz A, Crisa L, Schmitt C, Fournel S, King A, et al. HLA-G in the thymus: a subpopulation of medullary epithelial but not CD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein. Int Immunol. 1999;11:889–898
  11. Langat DK, Platt SJ, Tawfik O, Fazleabas AT, Hunt JS. Differential expression of human leukocyte antigen-G (HLA-G) messenger RNAs and proteins in normal human prostate and prostatic tumors. J Reprod Immunol. 2006;71:75–86
  12. Rouas-Freiss N, Moreau P, Ferrone S, Carosella ED. HLA-G proteins in cancer: do they provide tumor cells with an escape mechanism?. Cancer Res. 2005;65:10139–10144
  13. Hunt JS, Jadhav L, Chu W, Geraghty DE, Ober C. Soluble HLA-G circulates in mothers during pregnancy. Am J Obstet Gynecol. 2000;183:682–688
  14. Morales PJ, Pace JL, Platt JS, Phillips TA, Morgan K, Fazleabas AT, et al. Placental cell expression of HLA-G2 isoforms is limited to the invasive trophoblast phenotype. J Immunol. 2003;171:6215–6224
  15. Yao YQ, Barlow DH, Sargent IL. Differential expression of alternatively spliced transcripts of HLA-G in human preimplantation embryos and inner cell masses. J Immunol. 2005;175:8379–8385
  16. Hiby SE, King A, Sharkey A, Loke YW. Molecular studies of trophoblast HLA-G: polymorphism, isoforms, imprinting and expression in preimplantation embryo. Tissue Antigens. 1999;53:1–13
  17. Langat DK, Morales PJ, Fazleabas AT, Mwenda JM, Hunt JS. Baboon placentas express soluble and membrane-bound Paan-AG proteins encoded by alternatively spliced transcripts of the class Ib major histocompatibility complex gene, Paan-AG. Immunogenetics. 2002;54:164–173
  18. Hunt JS, Hsi BL, King CR, Fishback JL. Detection of class I MHC mRNA in subpopulations of first trimester cytotrophoblast cells by in situ hybridization. J Reprod Immunol. 1991;19:315–323
  19. Ober C, Aldrich C, Rosinsky B, Robertson A, Walker MA, Willadsen S, et al. HLA-G1 protein expression is not essential for fetal survival. Placenta. 1998;19:127–132
  20. Menier C, Riteau B, Dausset J, Carosella ED, Rouas-Freiss N. HLA-G truncated isoforms can substitute for HLA-G1 in fetal survival. Hum Immunol. 2000;61:1118–1125
  21. Solier C, Aguerre-Girr M, Lenfant F, Campan A, Berrebi A, Rebmann V, et al. Secretion of pro-apoptotic intron-4-retaining soluble HLA-G1 by human villous trophoblast. Eur J Immunol. 2002;32:3576–3586
  22. Ishitani A, Sageshima N, Lee N, Dorofeeva N, Hatake K, Marquardt H, et al. Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition. J Immunol. 2003;171:1376–1384
  23. Blaschitz A, Juch H, Volz A, Hutter H, Daxboeck C, Desoye G, et al. The soluble pool of HLA-G produced by human trophoblasts does not include detectable levels of the intron 4-containing HLA-G5 and HLA-G6 isoforms. Mol Hum Reprod. 2005;11:699–710
  24. Le Maoult J, Rouas-Freiss N, Carosella ED. HLA-G5 expression by trophoblast cells: the facts. Mol Human Reprod. 2005;11:719–722
  25. Le Bouteiller P. Human villous trophoblast and the lack of intron 4-retaining soluble HLA-G secretion: beware of possible methodological biases. Mol Hum Reprod. 2005;11:711–713
  26. Hunt JS, Geraghty DE. Soluble HLA-G isoforms: technical deficiencies lead to misinterpretations. Mol Human Reprod. 2005;11:715–717
  27. Sargent IL. Does “soluble” HLA-G really exist? Another twist to the tale. Mol Hum Reprod. 2005;11:695–698
  28. Sanders SK, Giblin PA, Kavathas P. Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts. J Exp Med. 1991;174:737–740
  29. Llano M, Lee N, Navarro F, Garcia P, Albar JP, Geraghty DE, 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. 1998;28:2854–2863
  30. King A, Allan DS, Bowen M, Powis SJ, Joseph S, Verma S, et al. HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. Eur J Immunol. 2000;30:1623–1631
  31. Rajagopalan S, Bryceson YT, Kuppusamy SP, Geraghty DE, van der Meer A, Joosten I, et al. Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol. 2006;4:e9
  32. Brown D, Trowsdale J, Allen R. The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens. 2004;64:215–225
  33. Boyson JE, Erskine R, Whitman MC, Chiu M, Lau JM, Koopman LA, et al. Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci USA. 2002;99:16180–16185
  34. Shiroishi M, Kuroki K, Ose T, Rasubala L, Shiratori I, Arase H, et al. Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J Biol Chem. 2006;281:10439–10447
  35. Shiroishi M, Kuroki K, Rasubala L, Tsumoto K, Kumagai I, Kurimoto E, et al. Structural basis for recognition of the non-classical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d). Proc Natl Acad Sci USA. 2006;103:16412–16417
  36. Petroff MG, Sedlmayr P, Azzola D, Hunt JS. Decidual macrophages are potentially susceptible to inhibition by class Ia and class Ib HLA molecules. J Reprod Immunol. 2002;56:3–17
  37. Yang Y, Geraghty DE, Hunt JS. Cytokine regulation of HLA-G expression in human trophoblast cell lines. J Reprod Immunol. 1995;29:179–195
  38. Chu W, Gao J, Murphy WJ, Hunt JS. A candidate interferon-gamma activated site (GAS element) in the HLA-G promoter does not bind nuclear proteins. Human Immunol. 1999;60:1113–1118
  39. Hunt JS, Langat DK, McIntire RH, Morales PJ. The role of HLA-G in pregnancy. Reprod Biol Endocrinol. 2006;4(Suppl. 1):S10
  40. Genbacev O, Joslin R, Damsky CH, Polliotti BM, Fisher SJ. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest. 1996;97:540–550
  41. Fournel S, Aguerre-Girr M, Huc X, Lenfant F, Alam A, Toubert A, et al. Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol. 2000;164:6100–6104
  42. Contini P, Ghio M, Merlo A, Poggi A, Indiveri F, Puppo F. Apoptosis of antigen-specific T lymphocytes upon the engagement of CD8 by soluble HLA class I molecules is Fas ligand/Fas mediated: evidence for the involvement of p56lck, calcium calmodulin kinase II, and Calcium-independent protein kinase C signaling pathways and for NF-kappaB and NF-AT nuclear translocation. J Immunol. 2005;175:7244–7254
  43. Le Rond S, Azema C, Krawice-Radanne I, Durrbach A, Guettier C, Carosella ED, et al. Evidence to support the role of HLA-G5 in allograft acceptance through induction of immunosuppressive/regulatory T cells. J Immunol. 2006;176:3266–3276
  44. McIntire RH, Morales PJ, Petroff MG, Colonna M, Hunt JS. Recombinant HLA-G5 and -G6 drive U937 myelomonocytic cell production of TGF-{beta}1. J Leukoc Biol. 2004;76:1220–1228
  45. Forte P, Pazmany L, Matter-Reissmann UB, Stussi G, Schneider MK, Seebach JD. HLA-G inhibits rolling adhesion of activated human NK cells on porcine endothelial cells. J Immunol. 2001;167:6002–6008
  46. Fons P, Chabot S, Cartwright JE, Lemfant F, L'Faqihi F, Giustiniani J, et al. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 on endothelial cells. Blood. 2006;108:2608–2615
  47. Pace JL, Morales PJ, Phillips TA, Hunt JS. Analysis of the soluble isoforms of HLA-G: mRNAs and proteins. In:  Soares MJ,  Hunt JS editor. Placental and trophoblast methods and protocols. Totowa: Humana Press; 2006;p. 181–203
  48. Langat DK, Morales PJ, Fazleabas AT, Hunt JS. Potential regulatory sequences in the untranslated regions of the baboon MHC class Ib gene, Paan-AG, more closely resemble those in the human MHC class Ia genes than those in the class Ib gene, HLA-G. Immunogenetics. 2004;56:657–666

PII: S0143-4004(07)00007-0

doi: 10.1016/j.placenta.2007.01.004

Placenta
Volume 28 , Pages S57-S63 , April 2007

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