Analysis of Ir gene control of cytotoxic response to hapten-modified self: Helper T cells specific for a sulfhydryl hapten can substitute for an anti-TNP-H-2^b self helper cell defect

Helper T cells specific for N-iodoacetyl-N'-(5-sulfonic 1-naphthyl) ethylene diamine (I-AED) were generated in (C56BL/6 x C3H/He)F₁ mice by immunization with I-AED-modified syngeneic cells (AED-self). The requirements for activation of hapten-induced helper cells were investigated. The results demonstrated that activation of AED and trinitrophenyl- (TNP) helper cells was strictly hapten specific. In addition, F₁ AED-helpers could be activated efficiently by either I-AED-modified H-2^b or H-2(k) self components to enhance the anti-AED self CTL responses. This contrasts with the previous findings demonstrating the failure of TNP-H-2^b self to activate F₁ TNP-helper cells. After AED-helpers were activated, they were capable of augmenting sensitization of cytotoxic T cells (CTL) against TNP-self. These results indicate that although the activation of hapten-reactive helper cells is antigen (hapten)-specific, the subsequent helper activity, as determined by augmentation of CTL responses against another hapten, is antigen nonspecific. Since helper function was antigen nonspecific, F₁ AED-helper cells activated by AED-H-2^b or AED-H-2(k) self were tested for their ability to augment the F₁ anti-TNP-H-2^b CTL response. The results indicate that the Ir gene defect in the ability of F₁ spleen cells to respond to TNP-H-2^b self could not be corrected by these helper cells. These results are discussed in the light of Ir gene controlled differences in the activation of AED and TNP-helper cells and possible models for augmenting CTL responses against various antigens in strains that generate marginal helper activity to TNP-self.