Antigen-specific elimination of T cells induced by oligomerized hemagglutinin (HA) 306-318

In a previous study we reported that oligomerized T cell epitopes "superact ivated" CD4(+) T cells. These oligomers, consisting of 12-16 copies of a pe ptide epitope derived from the hemagglutinin protein of influenza virus (HA 306-318), induced a specific T cell response in amounts as little as 5 pg/m l. We now show that the improved antigenicity of these multimerized epitope s can also be utilized to induce "high zone tolerance". Tolerization, simil ar to activation, occurred at about 3 logs lower concentration of oligomer than of peptide. HA306-318-specific T cell cultures became nonresponsive to stimulation with peptide after incubation with 0.5-5 mug/ml HA306-318 12-m er. The nonresponsiveness was accompanied by a drastic down-regulation of t he TCR and by T cell elimination by apoptotic cell death. In contrast, stim ulation with peptide even at 50 mug/ml led to temporary induction of anergy . Consequently, induction of tolerance with the oligomer was permanent and no recovery of the cultures was seen in recall experiments 12-14 days after high zone exposure to the 12-mer.