title: Tolerogenic function of dimeric forms of HLA-G recombinant proteins: a comparative study in vivo.
abstract: HLA-G is a natural tolerogenic molecule involved in the best example of tolerance to foreign tissues there is: the maternal-fetal tolerance. The further involvement of HLA-G in the tolerance of allogeneic transplants has also been demonstrated and some of its mechanisms of action have been elucidated. For these reasons, therapeutic HLA-G molecules for tolerance induction in transplantation are actively investigated. In the present study, we studied the tolerogenic functions of three different HLA-G recombinant proteins: HLA-G heavy chain fused to β2-microglobulin (B2M), HLA-G heavy chain fused to B2M and to the Fc portion of an immunoglobulin, and HLA-G alpha-1 domain either fused to the Fc part of an immunoglobulin or as a synthetic peptide. Our results demonstrate the tolerogenic function of B2M-HLA-G fusion proteins, and especially of B2M-HLA-G5, which were capable of significantly delaying allogeneic skin graft rejection in a murine in vivo transplantation model. The results from our studies suggest that HLA-G recombinant proteins are relevant candidates for tolerance induction in human transplantation.
authors.affiliation: CEA-I2BM-Service de Recherches en Hemato-Immunologie, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Favier
authors.forename: Kiave-Yune
authors.initials: KY
authors.lastname: HoWangYin
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.forename: Julien
authors.initials: J
authors.lastname: Caumartin
authors.forename: Marina
authors.initials: M
authors.lastname: Daouya
authors.forename: Anatolij
authors.initials: A
authors.lastname: Horuzsko
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
authors.forename: Joel
authors.initials: J
authors.lastname: LeMaoult
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016038:Skin Transplantation / Q000276:immunology
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D010455:Peptides; D011993:Recombinant Fusion Proteins