Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen-specific cytotoxic T lymphocytes.
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.
Oosten
Liesbeth E M
LE
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands. l.e.m.oosten@lumc.nl
Blokland
Els
E
van Halteren
Astrid G S
AG
Curtsinger
Julie
J
Mescher
Matthew F
MF
Falkenburg
J H Frederik
JH
Mutis
Tuna
T
Goulmy
Els
E
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
C110615:HA-1 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D007371:Interferon-gamma