An immunodominant minor histocompatibility alloantigen that initiates corneal allograft rejection.

Abstract

Murine orthotopic corneal allografts experience immune privilege and have good survival as compared with skin allografts. However, privilege is not complete, and some grafts are still rejected. Unexpectedly, corneas expressing minor histocompatibility (H) alloantigens are rejected at a higher rate than major histocompatibility complex (MHC) disparate grafts. We hypothesize that certain immunodominant minor H alloantigens are extremely immunogenic when expressed in corneal tissue, terminate ocular immune privilege, and initiate corneal allograft rejection. Corneal allograft survival and the role of CD4+ T cells and CD8+ T cells were examined in corneal transplants that expressed genetically defined minor H3 alloantigens. The H3 locus contains at least two minor H genes. H3a is presented by MHC class I and recognized exclusively by CD8+ T cells. H3b is presented by class II and recognized exclusively by CD4+ T cells. Congenic strains that differ from C57BL/10 at (1) H3a, (2) H3b, or (3) H3a+H3b were used for orthotopic corneal and skin transplants. Donor corneas expressing either H3a or H3a+H3b experienced immune privilege and survived longer than skin allografts. By contrast, donor corneas expressing H3b (recognized by CD4+ T cells) experienced vigorous rejection and were eliminated faster than skin allografts. There are minor H alloantigens that terminate ocular immune privilege and initiate corneal allograft rejection. These minor H alloantigens are more immunogenic when expressed in corneal tissue than when they are expressed in skin allografts.