Identification of a Novel HLA-A0201-restricted, Cytotoxic T Lymphocyte Epitope in a Human Glioma-associated Antigen, Interleukin 13 Receptor α2 Chain

Purpose: Interleukin 13 receptor α2-chain (IL-13Rα2) has been reported to be abundantly and specifically overexpressed in glioblastoma multiforme. Here we report the identification of a CTL epitope derived from the IL-13Rα2. Experimental Design: Mature dendritic cells (DCs) were pulsed with each of the synthetic peptides that were designed, based on a binding affinity-based prediction and a proteosomal cleavage site prediction system, and used to stimulate autologous CD8+ T cells from an HLA-A2+ healthy donor. After four to six cycles of restimulation, the immunoreactivity of the T cells was analyzed for specific IFN-γ production and CTL reactivity. Results: Of the five peptides tested, IL-13Rα 345–354 (WLPFGFILI) induced a CD8 + T-cell line that specifically produced IFN-γ in response to HLA-A2+ T2 cells pulsed with the relevant peptide and lysed these cells. Peptide titration assays demonstrated that half-maximal lysis of IL-13Rα 345–354 peptide-reactive CD8 + T cells required peptide loading concentration of ∼5 n m . Perhaps most importantly, this CD8 + T-cell line also displayed lytic activity against the HLA-A2+ human glioma cell lines that express IL-13Rα2. Conclusions: This novel CTL epitope may therefore serve as an attractive component of peptide-based vaccines to treat glioma and as a surrogate marker of T-cell immune responses in patients before and after therapy.