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INTRODUCTION: Cytotoxic T cells specific for the hematopoietic system-restricted minor histocompatibility antigens HA-1 and HA-2 are potential tools for the treatment of relapsed leukemia after minor histocompatibility antigen mismatched bone marrow transplantation. HA-1/HA-2-specific cytotoxic T cells with strong cytotoxic activity against HA-1/HA-2 positive target cells can be generated in vitro using HA-1 and HA-2 peptide-pulsed dendritic cells as antigen presenting cells. MATERIAL AND METHODS: We used HLA-A2 HA-1/HA-2 tetramers (HA-1(A2)/HA-2(A2) tetramers) to monitor the in vitro generation of HA-1- or HA-2-specific cytotoxic T cells. RESULTS: We show that the intensity of the tetramer-staining of the HA-1/HA-2-specific cytotoxic T cells strongly correlates with their capability to recognize mHag positive target cells. The bright tetramer-staining cytotoxic T cells lyse target cells expressing the natural ligand. The dim tetramer-staining cytotoxic T cells fail to lyse natural ligand positive target cells and lyse peptide-pulsed target cells only. The frequency of bright tetramer-staining, high avidity minor histocompatibility antigen-specific CTLs increases significantly upon appropriate antigen-specific restimulations. CONCLUSION: Our results demonstrate that HLA class I-minor histocompatibility antigen tetramers are useful tools for monitoring and selection of high avidity HA-1- and HA-2-specific cytotoxic T cells for adoptive immunotherapy.

Original publication

DOI

10.1038/sj/thj/6200065

Type

Journal article

Journal

Hematol J

Publication Date

2000

Volume

1

Pages

403 - 410

Keywords

Antigen Presentation, Biopolymers, Bone Marrow Transplantation, Cells, Cultured, Cytotoxicity, Immunologic, Graft vs Host Disease, Histocompatibility, Humans, Immunotherapy, Adoptive, Leukemia, Ligands, Minor Histocompatibility Antigens, Neoplasm Proteins, Oligopeptides, Peptide Fragments, T-Lymphocytes, Cytotoxic, Transplantation, Homologous