Different role of human HLA-DR and -DQ molecules in xenogeneic transplantation using transgenic mice

Background. The role of T lymphocytes in graft rejection in xenotransplanta tion is still unclear. The ability of the human HLA class II molecules DR a nd DQ to function as xenoantigens was investigated in a murine model of ski n grafting, using HLA-DR1 and -DQ6-transgenic mice. Methods. Skin from HLA-DR1- or -DQ6-transgenic mice was transplanted in con trol littermates. Spleen cells from donors or recipients were tested in mix ed lymphocyte reaction and cytotoxic assay. Results. Skin from HLA-DR1 transgenic mice was rejected and spleen cells fr om rejecting mice were able to proliferate to donor cells, although no reje ction was observed when the skin of HLA-DQ6-transgenic mice was engrafted i n control littermates. No cytotoxicity was observed in any models. Conclusions. Taken all together these results clearly suggest a hierarchy i n the xenogeneic potency of human HLA class II molecules, with the HLA-DR1 molecule functioning as a potent xenoantigen when compared with the HLA-DQ6 molecule.