HLA-G: Su importancia inmunológica

HLA-G: Su importancia inmunológica

HLA-G es una molécula clase I no clásica (Ib) del Complejo Mayor de Histocompatibilidad Humano (CMH), adopta siete isoformas, resultado del empalme alternativo de un mismo RNA inmaduro, cuatro se encuentran ligadas a la membrana (HLA-G1,-G2, -G3, -G4) y las otras tres formas son solubles (HLA-G5, - G6, -G7), teniendo en común el dominio extracelular a1. Se expresa de forma selectiva en la interfase materno fetal desempeñando un papel crucial en la inducción de un estado de tolerancia del feto semialogénico por el sistema inmune materno. Está molécula inhibe la citólisis de las NK mediante la interacción con uno o varios receptores inhibidores presentes en las NK (KIR), presenta un limitado polimorfismo, se han descrito 15 alelos, 14 de los cuales asignados por la nomenclatura del HLA. El HLA-G está asociado con algunas patologías en la gestación, tales como las infecciones intrauterinas; pre-eclampsia y en aborto recurrente espontáneo. Los estudios van dirigidos a controlar mejor las interacciones HLA-G/células NK en la inducción de un estado de tolerancia inmunitaria en el campo del transplante y la inmunología de los tumores.

1. Ober, C. HLA and pregnancy: The paradox of the allograft. Am J Hum Genet 1998; 62: 1-5.
2. Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R. A class I antigen, HLA-G, expressed in human trophoblast. Science 1990; 248: 220-3.
3. Geraghty DE, Koller BH, Orr HT. A Human Mayor Histocompatibility Complex class I gene that encodes a protein with a shortened cytoplasmatic segment. Proc Natl Acad Sci USA 1987; 84: 9145-9149.
4. Shukla M, Swaroop A, Srivastava R, Weissman S. The mRNA of a human class I gene HLA-G/HLA-6.0 exhibits a restricted pattern of expression. Nucleic Acids Res 1990; 18: 2189.
5. Mandelboim O, Pazmany L, Davis DM, Vales-Gomez M, Reyburn H, Rybalov B, Strominger JL. Multiple receptors for HLA-G on human natural killer cells. Proc. Natl. Acad. Sci. USA 1997; 94: 14666-14670.
6. Le Bouteiller P and Mallet V. HLA-G and pregnancy. Rev Reprod 1997; 2:7-13.
7. Carosella ED, Rouas-Freiss N, Pascale P, Dausset J. HLA-G: a tolerance molecule from the Mayor Histocompatibility Complex. Immunology Today 1999; 20: 60-62.
8. HLA Class I and II Sequence Alignments. January 2002 update. www.anthonynolan.org.uk/H16/seg/info.html .
9. Hugo Chromosome 6. Disease Loci and Genes www.abd.org/hugo/chr6 .
10. Hunt J, Petroff M, Morales P, Sedmayr P, Geraghty DE, Ober C. HLA-G in reproduction: Studies on the maternal- fetal interface. Hum Immunol 2000; 61: 1113-117.
11. Torres MI, Moreau P, Rouas-Freiss N, Dausset J, Carosella ED. HLA-G today. Inmunología 2001; 20: 18-29.
12. Carosella ED, Dausset J, Kirszenbaum M. HLA-G revisited. Immunology Today 1996; 17: 407-409.
13. Matte C, Lacaille J, Zijenah L, Ward B. The ZVITAMBO Study Group, and Roger M. HLA-G and HLA-E polymorphisms in an indigenous African population. Hum Immunol 2000; 61: 1150-1156.
14. 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.
15. Castro MJ, Morales P, Rojo-Amigo R, Martínez-Laso J, Allende L, Varela, García-Berciano M, Guillen-Perales J, Arnaiz-Villena A. 2000. Homozygous HLA-G*0105N healthy individuals indicate that membrane . anchored HLA-G1 molecule is not necessary for survival. Tissue Antigens 2000; 56: 232-239.
16. Van der Ven K, Ober C. 1994. HLA-G polymorphisms in African Americans. J Immunol 1994; 153:5628-5633
17. Kirszenbaum M, Djoulam S, Hors J, Le Gal I, De Oliviera EB, Prost S, Dausset J, Carosella E.D. 1997. HLA-G gene polymorphism segregation within CEPH reference families. Hum Immunol. 53: 140-147.
18. Le Bouteiller P, Blaschitz A. The functionality of HLA-G is emerging. Immunol Rev 1999; 167: 233-244.
19. Pascale P, Cabestre AF, Ibrahim E, Lefebvre S, Khalil-Daher I, Vazeux G, Moya RM, Bermond F, Dausset J, Carosella ED. Identification of HLA-G mRNA and expression of soluble HLA-G5, -G6, and .G7 transcripts in human transfected cells. Hum Immunol 2000; 61: 1138-1149.
20. Kirszenbaum M, Moreau P, Gluckman E Dausset J, Carosella ED. An alternatively spliced form of HLA-G mRNA in human trophoblast and evidence for the presence of HLA-G transcrip in adult lymphocytes. Proc Natl Acad Sci USA 1994; 91: 4209-4213.
21. Ishitani A, Geraghty D. Alternative Splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci USA 1992; 89: 3947-3951.
22. Fujii T, Ishitahi A, Geraghty DE. A soluble form of the HLAG antigen is encoded by a messenger ribonucleic acid containing intron 4. J Immunol 1994; 153: 5516. 5524.
23. Rouas-Freiss N, Marchal RE, Kirszenbaum M, Dausset J, Carosella ED. 1997. The alpha 1 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 USA 1997; 94: 5249-5254.
24. Rebmann V, Pfeiffer K, Päbler M, Ferrone S, Mainer S, Weiss E, Grosse-Wilde. H. Detection of HLA-G molecules in plasma and amniotic fluid. Tissue Antigens 1999; 53:14-22.
25. Pascale P, Rouas-Freiss N, Khalil-Daher I, Moreau P, Riteau B, Le Gal A, Avril M, Dausset J, Guillet J, Carosella ED. HLAG expression in melanoma: A way for tumor cells to scape from immunosurveillance. Proc Natl Acad Sci USA 1998; 95: 4510-4515.
26. Lila N, Carpentier A, Amrein C, Khlil-Daher I, Dausset J, Carosella ED. Implication of HLA-G molecule in hearthgraff acceptance. Lancet 2000; 355: 2138.
27. Carosella ED, Rouas-Freiss N, Paul P, Dausset J. Cómo escapa el feto a las defensas de su madre. Mundo Científico 1998; 190: 24 -26.
28. Le Bouteiller P, Solier C, Pröll J, Aguerre-Girr M, Fournel S, Lenfant F. Placental HLA-G protein expression in vivo: where and what for?. Hum Reprod Update 1999. 5: 223 -233.
29. Lanier L. Natural Killer cells fertile with receptors for HLAG?. Proc Natl Acad Sci USA. 1999; 96: 5343-5345.
30. Le Gal F, Riteau B, Sedlik C, Khalil-Daher I, Menier C, Dausset J, Guillet, J, Carosella ED, Rouas-Freiss N. HLA-G mediated inhibition of antigen-specific cytotoxic T lymphocytes. Int Immunol 1999 11:1351-1356.
31. Fournel S, Aguerre M, Huc X, Lenfant F, Alam A, Toubert A, Bensussan A, Le Bouteiller P. HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol 2000; 164: 6100-6104.
32. Le Bouteiller P. HLA-G in the human placenta: expression and potential functions. Biochem Soc Trans 2000; 28: 208-212.
33. Carosella ED. HLA-G: Fetomaternal tolerance. CR Acad Sci III 2000; 323: 675-680.
34. Rabreau M, Rouas-Freiss N, Landi M, Le Danff C, Carosella ED. HLA-G expression in trophoblast cells is independent of embryonic development. Hum Immunol 2000; 61: 1108-1112.
35. O.Brien M, McCarthy T, Jenkins D, Paul P, Dausset J, Carosella E.D, Moreau P. 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 2001; 58: 1943-1949.
36. O.Brien M, Dausset J, Carosella ED, Moreau P. Analysis of the role of HLA-G in preeclampsia. Hum Immunol 2000; 61: 1126-1131
37. Colbert GT, Chiang MH, Main EK. Expression of the nonclassical histocompatibility antigen HLA-G by preeclamptic placenta. Am J Obstet Gynecol 1994; 170(5): 1244 . 1250.
38. Goldman-Wohl DS, Ariel I, Greenfield C, Mochner-Celnikier D, Cross J, Fisher S, Yagel S. Lack of human leukocyte antigen G- expression in extravillous trophoblast is associated with pre-eclampsia. Mol Hum Reprod 2000; 6: 88-95.
39. Karhupoki J, Laitinen T, Tiilikainen AS. HLA-G polymorphism in Finish couples with recurrent spontaneous miscarriage. Bris J Obstet Gynaecol 1997; 104:1212-1214.
40. Penzes M, Rajczy K, Gyodi E, Réti M, Fehér É, Petrányi G. 1999. HLA-G gene polymorphism in the normal population and in recurrent spontaneous abortion in Hungary. Transplant. Proc. 31: 1832-1833
41. Yamashita T, Fujii T, Tokunaga K. Analysis of human leukocyte antigen-G polymorphism including intron 4 in
42. Japanese couples with habitual abortion. Am J Reprod Immunol 1999; 41:159-163.
43. Pfeiffer K, Fimmers R, Engels G, van der Ven H, van der Ven K. 2001. The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion. Mol Hum Reprod 2001; 7: 373-378.
44. Aldrich CL, Stephenson MD, Karrison T, Odem RR, Branch DW, Scott JR, Schreiber JR, Ober C. HLA genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. Mol Hum Reprod 2001; 7: 1167-1172.
45. Pascale P, Cabestré FA, Le Gal F, Khalil-Daher I, Le Danff C, Schmid M, Mercier S, Avril MF, Dausset J, Guillet J, Carosella E.D. Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies. Cancer Res 1999; 59: 1954-1960.
46. Onno M, Pangault C, Gaëlle LF, Guilloux V, Andre P, Fauchet R. Modulation of HLA-G antigens expression by human cytomegalovirus: specific induction in activated macrophages harboring human cytomegalovirus infection. J Immunol 2000. 164: 6426-6434.
47. Puppo F, Contini P, Ghio M, Indiveri F. Soluble HLA class I molecules/CD8 ligation trigger apoptosis of CD8+ cells by Fas/Fas-ligand interaction. Scientific World Journal 2002; 12: 2:421-3.
48. Hofmeister V, Weiss EH. 2003. HLA-G modulates immune responses by diverse receptor interactions. Semin Cancer Biol 2003; 13(5):317-23.
49. Hunt J, Vassmer D, Ferguson T, Miller L. Fas Ligand is positioned in mouse uterus and placenta to prevent trafficking of activated leukocytes between the mother and conceptus. J Immunol. 1997 158:4122-4128.