Here we present the first longitudinal study with HLA class II tetramers in patients with different outcomes of acute hepatitis C. We took advantage of an unusually immunodominant, HLA-DR1 restricted CD4+ T cell epitope which we had characterized in detail by specific CD4+ T cell clones from three different patients and which was complexed into an HLA-DR1 tetramer. The gene discussed is CD4; the disease is hepatitis C virus infection.