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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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IMMUNOBIOLOGY
Brief report

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, and Els Goulmy

From the 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; and Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.

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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