Haptens can serve as surrogate transplantation antigens in a manner that demonstrates H-2 restriction of graft rejection.

Hapten-immune mice are capable of rejecting syngeneic skin grafts that are derivatized with the relevant hapten, but only if the hapten is applied while the graft is "healing in." This model system was used to demonstrate that the hapten-specific immune effectors responsible for rejection are restricted by H-2 determinants of the recipient. Thus, haptens can be used in vivo as surrogate transplantation antigens for the study of immunopathogenic mechanisms in transplantation immunity.