title: Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen-specific cytotoxic T lymphocytes.
abstract: Cytotoxic T lymphocytes (CTLs) specific for hematopoietic-restricted minor histocompatibility antigens (mHags) are important reagents for adoptive immunotherapy of relapsed leukemia after allogeneic stem cell transplantation. However, expansion of these CTLs to therapeutic numbers is often hampered by the limited supply of antigen-presenting cells (APCs). Therefore, we evaluated whether cell-sized latex beads coated with HLA/mHag complexes HLA-A2/HA-1 or HLA-A2/HA-2 and recombinant CD80 and CD54 molecules can replace professional APCs. The artificial antigen-presenting constructs (aAPCs) effectively stimulated HA-1- and HA-2-specific CTL clones as shown by ligand-specific expansion, cytokine production, and maintenance of cytotoxic activity, without alteration of CTL phenotype. Furthermore, HA-1-specific polyclonal CTL lines were enriched as efficiently by aAPCs as by autologous HA-1 peptide-pulsed dendritic cells. Thus, aAPCs coated with HLA/mHag complexes, CD80, and CD54 may serve as tools for in vitro enrichment of immunotherapeutic mHag-specific CTL lines.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands. l.e.m.oosten@lumc.nl
authors.forename: Liesbeth E M
authors.initials: LE
authors.lastname: Oosten
authors.forename: Els
authors.initials: E
authors.lastname: Blokland
authors.forename: Astrid G S
authors.initials: AG
authors.lastname: van Halteren
authors.forename: Julie
authors.initials: J
authors.lastname: Curtsinger
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Mescher
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Tuna
authors.initials: T
authors.lastname: Mutis
authors.forename: Els
authors.initials: E
authors.lastname: Goulmy
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: C110615:HA-1 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D007371:Interferon-gamma