MHC class I and II antigens as targets of rejection in penetrating keratoplasty in low- and high-risk mouse eyes.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Osawa
Hideya
H
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Streilein
J Wayne
JW
D000818:Animals; D003315:Cornea / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D015948:Keratoplasty, Penetrating; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017354:Point Mutation; D013601:T-Lymphocytes / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II