Altered TCR ligands affect antigen-presenting cell responses: up-regulation of IL-12 by an analogue peptide.

When examining the effects of analogue peptides on changes in response patterns of a human Th0 clone DT13.2 that recognizes a peptide fragment (18RSLRTVTPIRMQGG31) derived from a group I allergen in Dermatophagoides farinae in the context of HLA-DQ6 (DQA10102/DQB10602), we found that replacement of the 21st residue Arg to Lys resulted in a significant increase in IFN-gamma production, with no remarkable changes either in proliferative response or IL-4 production, at high doses of the peptide. Selective enhancement of IFN-gamma production by the analogue peptide was accompanied by an increased production of IL-12, which was suppressed by an anti-IL-12 Ab down to the level of IFN-gamma production induced by the wild-type peptide. On the contrary, co-incubation with neutralizing Abs to IFN-gamma and IFN-gamma receptor did not affect IL-12 production, indicating that increased production of IL-12 stimulated by the analogue peptide was not due to an effect of IFN-gamma from T cells. Peptide-induced up-regulation of CD40 ligand expression at high peptide concentrations showed no difference between the wild-type and analogue peptides. These data collectively indicate that certain T cell/APC interactions mediated through TCR and altered TCR ligands affect APC responses and that signals transmitted to APC are as indispensable as those to T cells in determining T cell response patterns.