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 β2-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 lyric interactions with CTLs, and that HLA-G is involved in education of the lymphocytic repertoire of HLA-G transgenic mice.
Bibliographical noteFunding Information:
From the University of Minnesota, Lanna Huynh and Sandi Horn provided technical assistance, Dr. Julie Curtsinger and Dr. Matt Mescher provided advise on CTL assay protocols and provided facilities for performing these assays, Pat Taylor from Dr. Bruce Blazer’s lab provided instruction in skin graft technique, and Drs. Barbara Burke, Tami Lillemoe, and Dale Snover aided in the acquisition of human thymus samples. From the Mayo Clinic, Julie Hanson in Dr. Chella David’s lab provided assistance with initial HLA typing of the HLA-A2/G transgenic mice. Funding for these studies has been provided by NIH grants AI-18124 to H.T.O. and AI-08570 and AI-39828 to C.M.S. Funds for support of the transgenic facility at the University of Minnesota were provided by the Minnesota Medical Foundation and the University of Minnesota Graduate School. Funds for support of the animal care facility at the Muncie Center for Medical Education were provided by Ball State University.