HLA Tetramer Based Artificial Antigen-Presenting Cells Efficiently Stimulate CTLs Specific for Malignant Glioma.
OBJECTIVE
The interleukin-13 receptor alpha 2 (IL-13R alpha 2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. Here, we report a novel approach for targeting malignant glioma with IL-13R alpha 2-specific CTLs.


METHODS
Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen (HLA)-A2/pIL-13R alpha 2(345-354) tetrameric complexes, anti-CD28 antibody, and CD83 molecules to cell-sized latex beads, and used to stimulate IL-13R alpha 2-specific CTLs from the peripheral blood mononuclear cells of HLA-A2+ healthy donors. After multiple stimulations, the induced CTLs were analyzed for tetramer staining, IFN-gamma production, and CTL reactivity.


RESULTS
Tetramer staining assay showed that the induced CTLs specifically bound HLA-A2/pIL-13R alpha 2(345-354) tetramers. The CTLs specifically produced IFN-gamma in response to the HLA-A2/pIL-13R alpha 2(345-354)-aAPCs and exhibited specific lysis against T2 cells pulsed with the peptide pIL-13R alpha 2(345-354) and HLA-A2+ glioma cells expressing IL-13R alpha 2(345-354), whereas HLA-A2(-) glioma cell lines that express IL-13R alpha 2(345-354) could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-HLA class I monoclonal antibody.


CONCLUSIONS
The induced CTLs specific for IL-13R alpha 2(345-354) peptide could be a potential target of specific immunotherapy for HLA-A2+ patients with malignant glioma.
Jiang
Xiaobing
X
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. jxb917@126.com
Lu
Xiaoling
X
Liu
Ruen
R
Zhang
Fangcheng
F
Zhao
Hongyang
H
D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015870:Gene Expression; D005910:Glioma / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018106:CD28 Antigens; D006680:HLA Antigens; D007136:Immunoglobulins; D053663:Interleukin-13 Receptor alpha2 Subunit; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen