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Blood, 1 July 2005, Vol. 106, No. 1, pp. 144-149. Prepublished online as a Blood First Edition Paper on February 24, 2005; DOI 10.1182/blood-2004-07-2940.
Submitted July 29, 2004
University Children's Hospital Tubingen, Tubingen, Germany * Corresponding author; email: knschilb{at}med.uni-tuebingen.de.
Induction of cytotoxic T lymphocytes (CTLs) for treatment of relapsed leukemia after allogeneic stem cell transplantation is hindered by the laborious and time-consuming procedure of generating dendritic cells for antigen presentation. Artificial antigen-presenting cells (aAPCs) offer the advantage of being readily available in sufficient numbers, thus allowing for a highly standardized in vitro induction of CTLs. We generated aAPCs coated with anti-CD28-Ab and either high-density (HD) or low-density (LD) MHC class I molecules loaded with a nonapeptide derived from the hematopoiesis-restricted minor histocompatibility antigen HA-1H. HD- and LD-aAPCs potently induced HA-1H-specific CD8+ CTLs from untouched CD8+ T cells of healthy donors. CTLs were subsequently purified by magnetic activated cell sorting. HD- as well as LD-aAPC-induced CTLs exerted high HA-1H-specific cytotoxicity, resembled Tc1 effector memory cells, survived long time in vitro and were expanded by a factor varying between 8.2 and 51x104. T-cell receptor (TCR) repertoire of HA-1-tetramer+ CTLs was oligoclonal with a prominent usage of V
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