Graft-VS.-host-associated immune suppression is activated by recognition of allogeneic murine I-A antigens

Several combinations of F₁ hybrid mice were injected intravenously with parental spleen cells to determine the minimal H-2 differences between F₁ and parent that are necessary to induce graft-vs.-host-associated immune suppression (GVH-associated suppression). 7-14 d after injection, the spleens of the F₁ mice were tested for cytotoxic T lymphocyte potential by in vitro sensitization against trinitrophenyl-self and H-2 alloantigens. The results indicate that parenal T lymphocytes must recognize I-A allogeneic determinants of the F₁ recipient in order to induce suppression. Recognition of K or D alone or D with I region products other than I-A did not induce suppression. The recognition of I region without K and/or D and even the I-A difference between C57BL/6 and the B6.C^bm12 mutation resulted in immune suppression that was as potent as that resulting from the recognition of K, D, and I together. The possible significance of this function for I-A antigens is discussed with respect to three clinical examples of immune suppression for which this phenomenon may be relevant.