The priming of cytotoxic T-cell precursors is strictly helper T cell-dependent.

Allogeneic chimaeras that utilize C.B-17 SCID mice (H-2d) as recipients of MHC mismatched bone marrow from C57B1/6 (H-2b) or SJL/J (H-2s) mice have been used to provide experimental evidence demonstrating the necessity for a direct interaction between an effector T helper and the cytotoxic T-cell precursor in order to generate cytotoxic effector T cells specific for the minor histocompatibility (H) antigens of DBA/2 (H-2d) mice. No effect of helpers specific for antigen-processed or not-presented on antigen-presenting cells could be observed. Allo-chimaeras that contain T cells bearing H-2s, and which are restricted to H-2d, make a cytotoxic T-cell response to minor H antigens which is H-2d restricted if, and only if, cloned anti-H-2s effector T helpers are present during the in vivo priming step. Cloned anti-H-2d effector helpers, which are without effect in the allo-chimaeras, do provide a strong helper activity when tested in normal H-2d mice. These findings cannot be reconciled with a strict single recognitive model of restrictive antigen recognition, but they are consistent with a dual recognitive model, which incorporates many of the features of the single recognitive model.