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Blood, 1 July 2004, Vol. 104, No. 1, pp. 224-226.
Prepublished online as a Blood First Edition Paper on March 18, 2004; DOI 10.1182/blood-2003-07-2461.


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Submitted July 21, 2003
Accepted February 18, 2004

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

Liesbeth E Oosten*, Els Blokland, Astrid G van Halteren, Julie Curtsinger, Matthew F Mescher, J H Falkenburg, Tuna Mutis, and Els Goulmy

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Center of Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

* Corresponding author; email: l.e.m.oosten{at}lumc.nl.

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 human leukocyte antigen (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 (DCs). Thus, aAPCs coated with HLA/mHag complexes, CD80 and CD54 may serve as tools for in vitro enrichment of immunotherapeutical mHag-specific CTL lines.


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