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Identification of a Novel HLA-A*0201-restricted, Cytotoxic T Lymphocyte Epitope in a Human Glioma-associated Antigen, Interleukin 13 Receptor 2 Chain¹

Departments of Surgery [F. O., W. J. S., H. O.], Pathology [W. H. C.], and Neurological Surgery [I. F. P., H. O.], University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, and Toray Industries, Inc., Chemicals Research Laboratories, Nagoya 455-8502, Japan [F. O.]

Purpose: Interleukin 13 receptor 2-chain (IL-13R2) 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-13R2.

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- production and CTL reactivity.

Results: Of the five peptides tested, IL-13R_345–354 (WLPFGFILI) induced a CD8⁺ T-cell line that specifically produced IFN- 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-13R_345–354 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-13R2.

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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