Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen-specific cytotoxic T lymphocytes.

Liesbeth E M Oosten; Els Blokland; Astrid G S van Halteren; Julie Curtsinger; Matthew F Mescher; J H Frederik Falkenburg; Tuna Mutis; Els Goulmy

doi:10.1182/blood-2003-07-2461

PubMed · 15031203

Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen-specific cytotoxic T lymphocytes.

Liesbeth E M Oosten·Els Blokland·Astrid G S van Halteren·Julie Curtsinger·Matthew F Mescher·J H Frederik Falkenburg·Tuna Mutis·Els Goulmy

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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.

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Antigen Presentation Antigen-Presenting Cells Cell Division Cell Line Clone Cells Cytotoxicity, Immunologic Dendritic Cells HLA-A2 Antigen Herpesvirus 4, Human Humans Interferon-gamma Minor Histocompatibility Antigens Oligopeptides T-Lymphocytes, Cytotoxic T-Lymphocytes, Helper-Inducer Journal Article Research Support, Non-U.S. Gov't

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Liesbeth E M Oosten, Els Blokland, Astrid G S van Halteren, Julie Curtsinger, Matthew F Mescher, J H Frederik Falkenburg, Tuna Mutis, Els Goulmy. 2004-03-18. Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen-specific cytotoxic T lymphocytes.. https://doi.org/10.1182/blood-2003-07-2461

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