HLA class I-minor histocompatibility antigen tetramers select cytotoxic T cells with high avidity to the natural ligand

Geraldine Gillespie, Tuna Mutis, Ellen Schrama, Janine Kamp, Bennie Esendam, J. H.Frederik Falkenburg, Els Goulmy, Paul Moss

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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-1A2/HA-2A2 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-specifc 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 languageEnglish
Pages (from-to)403-410
Number of pages8
Journalhematology journal
Issue number6
Publication statusPublished - 1 Jan 2000


  • Adoptive immunotherapy
  • Cytotoxic T cells
  • MHC-peptide tetramers
  • Minor histocompatibility antigens

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