Poly(Glu50Tyr50) (GT) is not immunogenic in most inbred mouse strains. GT injection produces an I-J--bearing, GT-specific T-cell--derived suppressor factor (GT-TsF1) in H-2b,d,k haplotype mice. GT-TsF1 generates second-order suppressor T cells (Ts2) in H-2a,d,k haplotype mice. Here, we show that in order for GT-TsF1 to act, the recipient strain must express I-E molecules. This suggests that T cells are not the primary target of GT-TsF1. GT-TsF1 can be presented by Ia+ A20-2J B lymphoma cells. GT-TsF1 presentation is blocked by anti-I-E, but not by anti--I-A, mAb, whereas GAT presentation is blocked by anti-I-A, but not by anti--I-E, mAbs. These data suggest that I-J recognizes (or is recognized by) I-E. The existence and role of I-J molecules in immune regulation are discussed in light of these data.

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