Cytotoxic T lymphocyte recognition of HLA-G in mice.
Several features of HLA-G's sequence and expression pattern distinguish HLA-G from its classical counterparts. These features, including HLA-G's limited polymorphism and its expression at the maternal-fetal interface, have been used as a basis for suggesting a distinct functional role for this nonclassical class I HLA molecule. On the other hand, published data do demonstrate that HLA-G has much in common with its classical counterparts. It associates with beta 2-microglobulin and cytosolic peptides, it binds to CD8, and its presence can inhibit NK-cell-mediated lysis of HLA-G-bearing target cells. To develop a model in which HLA-G's function could be more thoroughly studied, we produced several HLA-G-expressing transgenic mouse strains. We report here the results of skin graft experiments which show that nontransgenic mice reject HLA-G-expressing transgenic murine skin as foreign and that this rejection is associated with the presence in the recipient of lymphocytes capable of specifically lysing HLA-G-expressing cells. In addition, experiments are described which demonstrate that HLA-G transgenic mice recognize HLA-G as a "self" molecule. Together the reported data demonstrate that HLA-G is capable of stimulating an HLA-G-restricted CTL response, that HLA-G molecules can serve as target molecules in lytic interactions with CTLs, and that HLA-G is involved in education of the lymphocytic repertoire of HLA-G transgenic mice.
Schmidt
C M
CM
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
Garrett
E
E
Orr
H T
HT
D000328:Adult; D000818:Animals; D006680:HLA Antigens / Q000235:genetics / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger