Evidence that major histocompatibility complex restriction of foreign transplantation antigens occurs when tolerance is induced in neonatal mice and rats.

Studies on the survival of skin-specific antigen (Skn)-incompatible skin grafts in mice rendered tolerant at birth with major histocompatibility complex (MHC)-incompatible lymph node and spleen or bone marrow cells, as well as studies concerned with the survival of third-party skin grafts in rats rendered tolerant at birth with MHC-incompatible bone marrow cells, indicate that MHC restriction of foreign transplantation antigens occurs when tolerance is induced. Thus, evidence is presented that animals rendered tolerant with MHC-incompatible bone marrow cells depleted of mature T lymphocytes will accept any graft that is homozygous for the bone marrow donor's foreign MHC. Evidence has also been obtained that continuous exposure to foreign transplantation antigens in association with an MHC different from that of the graft may induce unresponsiveness to the same antigens in association with the MHC of the graft.