Altered peptide ligands and wild-type peptide induce indistinguishable responses of a human Th0 clone.

The response of the human influenza hemagglutinin (HA)-specific T helper clone HA1.7 to its wild-type (wt) HA307-319 peptide ligand and related altered peptide ligands (APL) was examined over a wide range of antigen concentrations. The time course of cytokine production and surface expression of CD40 ligand and CD3 was followed at the single-cell level by flow cytometry and compared with the induction of proliferation. We observed that the APL induced responses that were indistinguishable from those induced by the wt HA ligand, albeit at higher antigen densities. Moreover, the activation parameters were induced with identical kinetics. Blocking of CD4 co-ligation inhibited the recognition of the weakly stimulatory APL, but not of the wt HA307-319 peptide. Finally, in all cases the response of the T cell clone correlated with down-regulation of surface TCR/CD3 complexes. Together, these observations support a quantitative model of T cell activation.