title: Induction of the Epstein-Barr virus latent membrane protein 2 antigen-specific cytotoxic T lymphocytes using human leukocyte antigen tetramer-based artificial antigen-presenting cells.
abstract: Cytotoxic T lymphocytes (CTLs) specific for the Epstein-Barr virus (EBV) latent membrane protein 2 (LMP2) antigen are important reagents for the treatment of some EBV-associated malignancies, such as EBV-positive Hodgkin's disease and nasopharyngeal carcinoma. However, the therapeutic amount of CTLs is often hampered by the limited supply of antigen-presenting cells. To address this issue, an artificial antigen-presenting cell (aAPC) was made by coating a human leukocyte antigen (HLA)-pLMP2 tetrameric complex, anti-CD28 antibody and CD54 molecule to a cell-sized latex bead, which provided the dual signals required for T cell activation. By co-culture of the HLA-A2-LMP2 bearing aAPC and peripheral blood mononuclear cells from HLA-A2 positive healthy donors, LMP2 antigen-specific CTLs were induced and expanded in vitro. The specificity of the aAPC-induced CTLs was demonstrated by both HLA-A2-LMP2 tetramer staining and cytotoxicity against HLA-A2-LMP2 bearing T2 cell, the cytotoxicity was inhibited by the anti-HLA class I antibody (W6/32). These results showed that LMP2 antigen-specific CTLs could be induced and expanded in vitro by the HLA-A2-LMP2-bearing aAPC. Thus, aAPCs coated with an HLA-pLMP2 complex, anti-CD28 and CD54 might be promising tools for the enrichment of LMP2-specific CTLs for adoptive immunotherapy.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Lu
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Liang
authors.forename: Cai-E
authors.initials: CE
authors.lastname: Zhang
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Lu
authors.forename: Xiu-Fang
authors.initials: XF
authors.lastname: Weng
authors.forename: Xiong-Wen
authors.initials: XW
authors.lastname: Wu
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy*; D006680:HLA Antigens / Q000737:chemistry / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000276:immunology; D006689:Hodgkin Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000737:chemistry / Q000276:immunology*; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D014763:Viral Matrix Proteins; D018799:Intercellular Adhesion Molecule-1