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 help er clone HA1.7 to its wild-type (wt) HA307-319 peptide ligand and rela ted altered peptide ligands (APL) was examined over a wide range of an tigen concentrations. The time course of cytokine production and surfa ce expression of CD40 ligand and CD3 was followed at the single-cell l evel by flow cytometry and compared with the induction of proliferatio n. We observed that the APL induced responses that were indistinguisha ble from those induced by the wt HA ligand, albeit at higher antigen d ensities. Moreover, the activation parameters were induced with identi cal kinetics. Blocking of CD4 co-ligation inhibited the recognition of the weakly stimulatory APL, but not of the wt HA307-319 peptide. Fina lly, in all cases the response of the T cell clone correlated with dow n-regulation of surface TCR/CD3 complexes. Together, these observation s support a quantitative model of T cell activation.