Regulation of immune responses by I-J gene products. IV. Distinct suppressor factors derived from "nonsuppressor" A strain mice.

A/J, A/WySn (H-2a, I-Jk), and B6 (H-2b, I-Jb) mice are poly(Glu50Tyr50)(GT) nonresponders. GT preimmunization does not suppress humoral immune responses to the immunogenic form of GT, GT-MBSA (GT-methylated bovine serum albumin), in these strains. B6 mice produce an idiotypic GT-specific T cell-derived suppressor factor (GT-TsF1) after GT injection, but cannot be suppressed by this or any other GT-TsF1. H-2a mice do not produce GT-TsF1, but can be suppressed by B6 GT-TsF1. Injection of cellfree B6 GT-TsF1 into H-2a mice leads to the production of two distinct I-Jk GT-TsF. We have termed these GT-TsF2 and GT-TsF3 on the basis of their kinetic activity and antigenic markers. Anti-idiotypic I-Jk GT-TsF2 is suppressive at a time intermediate between GT-TsF1 and GT-TsF3. Idiotypic I-Jk GT-TsF3 suppresses GT-MBSA PFC responses the day of PFC assay. GT-TsF3, not GT-TsF1, suppresses B6 GT-MBSA PFC responses, indicating that these idiotypic factors are distinct. Our results establish that H-2a lack or have a defective Ts1 cell for GT suppression, and H-2b mice lack a functional Ts2 cell. These findings offer strategies for circumventing suppressor T cell defects in "nonsuppressors."