HLA-G transgenic mice: a model for studying expression and function at the maternal/fetal interface.
Experiments designed to identify all HLA class I genes led to the cloning of the HLA-G gene (Geraghty et al. 1987). Very low levels of HLA-G mRNA expression have been demonstrated in the eye, thymus, peripheral blood lymphocytes and in keratinocytes (Shukla et al. 1990, Ishitani & Geraghty 1992, Kirszenbaum et al. 1994, Ulbrecht et al. 1994). Higher levels of HLA-G expression were demonstrated in certain subpopulations of trophoblasts (Ellis et al. 1990, Kovats et al. 1990). Specifically, those subpopulations of trophoblasts in direct contact with decidua, i.e. the cytotrophoblasts of the cytotrophoblast shell and columns, invasive cytotrophoblasts, and cytotrophoblasts of the chorionic membrane, express HLA-G (Yelavarthi et al. 1991, Chumbley et al. 1993). HLA-G molecules on these cells are in a position to interact directly with the maternal immune system. HLA-G transgenic mice have been produced in an effort to produce a model in which antigen presentation by HLA-G can be studied. Studies utilizing these transgenic mice have led to the definition of a previously unknown regulatory region and have yielded some basic information about HLA-G's ability to function as a class I molecule (Schmidt et al., in press; manuscript in preparation). One of the HLA-G transgenic mouse lines produced, G.3.2, has been shown to have a cell-type specific extraembryonic HLA-G expression pattern paralleling that seen in human extraembryonic tissues (Schmidt et al, in press). In addition, the levels of HLA-G mRNA expression seen in the extraembryonic tissues from this transgenic mouse line are similar to the levels of HLA-G mRNA expression detectable in human extraembryonic tissues. As cells expressing HLA-G come in direct contact with decidual cells, these mice will serve as a model in which HLA-G's ability to present foreign antigens to the maternal immune system can be studied. The G.3.2 HLA-G transgenic mouse line also exhibits thymic HLA-G expression levels similar to those seen in human thymus (Schmidt et al., manuscript in preparation). HLA-G expression in the transgenic murine thymus is largely restricted to dendritic cells. It is possible that this thymic HLA-G mRNA expression is responsible for the tolerance to HLA-G which is seen in the HLA-G transgenic mice. Further studies will be necessary to determine whether the lymphocytic repertoire of the HLA-G transgenic mouse can recognize HLA-G molecules presenting foreign peptides.
Schmidt
C M
CM
Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis 55455, USA.
Orr
H T
HT
D000818:Animals; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D008431:Maternal-Fetal Exchange / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D011247:Pregnancy
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I