FIG.4.

High functional avidity of antigen-specific responses to the autologous epitope, PR82V_76-84, or PR82A_76-84 detected in PBMC of HLA-A2-positive individuals. The range of peptide concentrations at which 50% maximal IFN-γ responses were reached is indicated with gray bars illustrating the interpatient range of functional avidity detected to an epitope. (a) A high functional avidity was detected to the autologous epitope PR82V_76-84 epitope in three patients with a wild-type Val at position 82. (b) An extremely low functional avidity was detected to the mutant PR82A_76-84 peptide in one of these patients. In the other patient (3153.1) the difference between the avidities was less pronounced, with functional avidities of 0.40 nM to the wild-type peptide and 0.80 nM to the mutant peptide. (c) In patients with the Val-to-Ala mutation at position 82, the response to the PR82V_76-84 epitope ranged from high to extremely low. (d) These patients had developed a high-avidity response to the mutant peptide. To further measure the functional avidity to other epitopes of different HLA restrictions, we studied avidity to other epitopes. (e to g) The functional avidity was shown to be of intermediate strength to the RT_158-66 epitope (50% maximal response, 15 nM) (e), intermediate to the Gag_162-172 epitope (50% maximal response range, 20 to 30 nM) (f), and high to the CMV pp65 epitope (50% maximal response range, 1 to 5 nM) (g).