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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 xenotransplantation is still unclear. The ability of the human HLA class II molecules DR and DQ to function as xenoantigens was investigated in a murine model of skin grafting, using HLA-DR1 and -DQ6-transgenic mice.
Methods:
Skin from HLA-DR1- or -DQ6-transgenic mice was transplanted in control littermates. Spleen cells from donors or recipients were tested in mixed lymphocyte reaction and cytotoxic assay.
Results:
Skin from HLA-DR1-transgenic mice was rejected and spleen cells from rejecting mice were able to proliferate to donor cells, although no rejection was observed when the skin of HLA-DQ6-transgenic mice was engrafted in control littermates. No cytotoxicity was observed in any models.
Conclusions:
Taken all together these results clearly suggest a hierarchy in 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.