HLA-G functions as a restriction element and a transplantation antigen in mice

Anatolij Horuzsko, Jane Antoniou, Peter Tomlinson, Vera Portik-Dobos, Andrew L. Mellor

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)645-653
Number of pages9
JournalInternational Immunology
Volume9
Issue number5
DOIs
StatePublished - Jun 11 1997

Keywords

  • Human class I-like protein HLA-G
  • MHC restriction
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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