CYTOTOXIC T-LYMPHOCYTE RECOGNITION OF HLA-G IN MICE

Several features of HLA-G's sequence and expression pattern distinguis h HLA-G from is classical counterparts. These features, including HLA- G's limit ed polymorphism and its expression at the maternal-fetal int erface, have been used as a basis for suggesting a distinct functional role for this nonclassical class I HLA molecule. On the other hand, p ublished data do demonstrate that HLA-G has much in common with its cl assical counterparts. It associates with beta 2-microglobulin and cyto solic 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 wh ich HLA-G's function could be more thoroughly studied, we produced sev eral HLA-G-expressing transgenic mouse strains. We report here the res ults of skin graft experiments which show that nontransgenic mice reje ct-HLA-G-expressing transgenic murine skin as foreign and that this re jection is associated with the presence in the recipient of lymphocyte s 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 de monstrate 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 th e lymphocytic repertoire of HLA-G transgenic mice. (C) American Societ y for Histocompatibility and Immunogenetics, 1997. Published by Elsevi er Science Inc.