The role of major and minor histocompatibility antigens in orthotopic corneal transplantation in mice.

The mouse model of orthotopic corneal transplantation was used to evaluate the clinical course of corneal graft rejection process. Corneal grafts were placed into eyes of naive, unmodified recipients or recipients presensitized with skin graft two weeks before corneal transplantation. Two strain combinations were used, one with genetic disparity at both major and minor histocompatibility antigens and the other with the difference only at multiple minor histocompatibility antigens. A panel of syngeneic graft recipients served as controls. In naive recipients, rejection reaction was recorded in more than 90% of recipients mostly during the third week after grafting and 40-50% of corneas displayed irreversible failure in both strain combinations. Both MHC compatible and incompatible corneal grafts in all presensitized recipients were irreversibly rejected by a second-set allograft reaction. The results thus show an important role of multiple minor histocompatibility antigens in corneal allotransplantation in mice. In addition, the prompt reaction in presensitized recipients is evidence for expression of allotransplantation immunity in the eye, which has been for a long time considered as a privileged site sequestered from systemic immunity.