Non-MHC antigens and their relative resistance to immunosuppression after corneal transplantation

We have used a high responder rat model to examine the role that non-MHC antigens play in corneal graft rejection. Recipients were backcross animals derived from a cross between two inbred strains, which mimicked the human outbred population in that donor and recipient could be matched or mismatched for MHC antigens, while non-MHC mismatches were variable and unknown. All mismatched grafts and 87% of matched grafts were rejected (median survival 11 and 17 days respectively). The high incidence of rejection of matched grafts indicates that several independently segregating non-MHC genes play a role in rejection. Moreover, the immune response to matched grafts appeared resistant to immunosuppression, suggesting that matching does not permit reduced dosage of immunosuppressants. A mechanism is discussed whereby matching at the class II locus may enhance presentation of mismatched histocompatibility antigens or viral peptides derived from infected graft cells, thereby prejudicing graft survival.