Identification of a novel HLA-A* 0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor α2 chain
F Okano, WJ Storkus, WH Chambers, IF Pollack… - Clinical Cancer …, 2002 - AACR
F Okano, WJ Storkus, WH Chambers, IF Pollack, H Okada
Clinical Cancer Research, 2002•AACRAbstract 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 …
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 …
Abstract
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-13Rα345–354 (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-13Rα345–354 peptide-reactive CD8+ T cells required peptide loading concentration of ∼5 nm. 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.
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