The Role of Minor Histocompatibility Alloantigens in Penetrating Keratoplasty

To review the experimental evidence that implicates minor histocompatibility (H) antigens in the vulnerability of orthotopic corneal transplants to rejection, and to speculate on the possible role of minor H antigens in penetrating keratoplasty in humans.Orthotopic corneal transplantations have been conducted in numerous inbred strains of mice and rats, and the fate of these grafts, as well as the immune responses mounted by recipients, have been examined in vivo and in vitro.Minor H antigens have been found to be more important barriers to the success of orthotopic corneal transplants in rodents than have grafts disparate at the major histocompatibility complex (MHC). The reasons for this reversal of the immunogenetic rules of transplantation reflect unique features of the cornea with respect to (a) expression of MHC-encoded molecules, (b) content of class II MHC-bearing antigen presenting cells, (c) vulnerability to rejection by direct alloreactive T cells, and (d) existence of ocular immune privilege.Since minor H antigens are the major barriers to acceptance of orthotopic corneal allografts in rodents, minor H antigens should be considered as important targets of rejection in failed penetrating keratoplasty in humans.