Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain.
OBJECTIVE
Interleukin 13 receptor alpha2-chain (IL-13Ralpha2) 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-13Ralpha2.


METHODS
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-gamma production and CTL reactivity.


RESULTS
Of the five peptides tested, IL-13Ralpha(345-354) (WLPFGFILI) induced a CD8(+) T-cell line that specifically produced IFN-gamma 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-13Ralpha(345-354) peptide-reactive CD8(+) T cells required peptide loading concentration of approximately 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-13Ralpha2.


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.
Okano
Fumiyoshi
F
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Storkus
Walter J
WJ
Chambers
William H
WH
Pollack
Ian F
IF
Okada
Hideho
H
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D014408:Biomarkers, Tumor; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005910:Glioma / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D018123:Receptors, Interleukin / Q000737:chemistry / Q000276:immunology*; D053660:Receptors, Interleukin-13; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology; D019444:Vaccines, DNA
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000939:Epitopes; D015789:HLA-A2 Antigen; C508181:IL13RA1 protein, human; D053661:Interleukin-13 Receptor alpha1 Subunit; D010446:Peptide Fragments; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019444:Vaccines, DNA