MHC Class I and II Antigens as Targets of Rejection in Penetrating Keratoplasty in Low- and High-Risk Mouse Eyes

Abstract

To determine the extent to which expression of major histocompatibility complex (MHC) class I and II molecules contributes to rejection of orthotopic corneal transplants in mice. Full-thickness corneas, prepared from eyes of normal C57BL/6 (B6) and BALB/c mice and from B6 mice in which the class II gene I-A or the beta2-microglobulin (beta2mu) gene was disrupted, were placed orthotopically in low- or high-risk eyes of BALB/c (fully incompatible), BALB.B [minor histoincompatible (H) only], and bm12 (class II only disparate) recipients. BALB/c grafts were placed in low-risk eyes of normal B6 and B6 mice with disrupted H-2 DMalpha genes. Graft survival was judged by clinical examination. Recipient-identical class II, but not class I, molecules on fully allogeneic corneas grafted to low-risk beds promoted graft rejection. Allogeneic class II molecules on fully allogeneic corneas placed in high-risk beds promoted graft rejection more strongly than did allogeneic class I molecules. Neither allogeneic class I molecules nor recipient-identical class II molecules on grafts placed in high-risk beds contributed to graft outcome. Mice deficient in H-2 DMalpha failed to reject fully incompatible cornea grafts. On corneal allografts, where minor H antigens are the major barriers to acceptance, allogeneic class II molecules promote rejection if the graft is placed in high-risk eyes, whereas recipient-type class II molecules promote rejection if the graft is placed in low-risk eyes. Allogeneic class I molecules make a minor contribution to rejection only if the grafts are placed in high-risk eyes.