HLA-G functions as a restriction element and a transplantation antigen in mice.
HLA-G, a human MHC class I molecule expressed on the trophoblast during pregnancy, was expressed in transgenic mice by recombining the HLA-G gene with a transcriptional promoter from a murine H-2 MHC class I gene. Skin grafts from HLA-G transgenic mice were rejected by non-transgenic mice showing that HLA-G behaves as a xenotransplantation antigen in mice. Further investigation revealed that murine T cells recognize native HLA-G directly as a xenoantigen or they recognize processed peptides derived from HLA-G presented in the context of murine MHC molecules. HLA-G molecules also function as restriction elements capable of presenting peptides to murine T cells since immunization of HLA-G transgenic mice with peptide that binds specifically to HLA-G molecules elicited HLA-G-restricted, cytotoxic T cell responses. In addition, murine T cell responses to human xenoantigens are enhanced when responder cells originated from HLA-G transgenic mice. Based on these observations, we conclude that expression of HLA-G molecules influences selection of the murine T cell repertoire and that HLA-G exhibits immunological properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice. Thus, any unique immunological functions mediated by HLA-G must arise from the distinctive, trophoblast-specific pattern of HLA-G expression in humans and not from structural peculiarities of HLA-G molecules.
Horuzsko
A
A
Division of Molecular Immunology, National Institute for Medical Research, London, UK.
Antoniou
J
J
Tomlinson
P
P
Portik-Dobos
V
V
Mellor
A L
AL
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015478:Antigens, Heterophile; D000939:Epitopes; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I