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

In a previous study we reported that oligomerized T cell epitopes "superactivated" CD4+ T cells. These oligomers, consisting of 12–16 copies of a peptide epitope derived from the hemagglutinin protein of influenza virus (HA306–318), induced a specific T cell response in amounts as little as 5 pg/ml. We now show that the improved antigenicity of these multimerized epitopes can also be utilized to induce "high zone tolerance". Tolerization, similar 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 μg/ml HA306–318 12‐mer. The nonresponsiveness was accompanied by a drastic down‐regulation of the TCR and by T cell elimination by apoptotic cell death. In contrast, stimulation with peptide even at 50 μg/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.