Regulation of immune responses by I-J gene products. II. Presence of both I-J(b) and I-J(k) suppressor factors in (nonsuppressor X nonsuppressor)F₁ mice

Antigen-specific suppression to poly(Glu⁵⁰-Tyr⁵⁰) (GT) is under the control of two complementary immune suppressor (Is) genes located in the major histocompatibility (H-2) complex of the mouse. Suppressor stains of mice produce both suppressor T (Ts) cells and Ts-derived suppressor factors (TsF) that bear antigenic determinants of the I-J subregion of the H-2 complex. Nonsuppressor strains of mice, on the other hand, are not suppressed by GT preimmunization. These nonsuppressor mice, however, can be classified according to those that lack the ability to make GT-specific T cell-derived suppressor factor (GT-TsF) after GT injection (i.e., H-2(a), I-J(k) mice) and those that lack the ability to be suppressed by the appropriate GT-TsF (i.e., H-2(b,g2), I-J(b) mice). In the present study, we demonstrate that (H-2(a) X H-2(b,g2)F₁ hybrid mice produce distinct GT-specific suppressor factors of both parental I-J haplotypes. Moreover, only the I-J(b)-bearing GT-TsF derived from these F₁ hybrid mice is able to induce second-order suppressor cells (T(s)₂). This is consistent with the observation that injection of GT-TsF₁ derived from C57BL/6 (I-J(b)) mice into A/j (I-J(k)) mice leads to the production of an antigen-specific I-J(k) GT-TsF₂. Our results suggest that Is gene complementation occurs through a different cellular mechanism than was previously observed for Ir gene complementation. Further, we show that complementing (nonsuppressor X nonsuppressor)F₁ hybrid mice produce an I-J(b) (and not an I-J(k) GT-TsF₁ and an I-J(k) (not an I-J(b)) GT-TsF₂, thus suggesting a heterogeneity of Ia loci within the I-J subregion. Data presented in the present study suggest that there may be even more heterogeneity within the I-J subregion than has been heretofore reported with regard to I-J expression on Ts.