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

The Hematology Journal : the Official Journal of the European Haematology Association
G GillespiePaul A Moss

Abstract

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. 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. 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. Our results demonstrate that HLA class I-minor...Continue Reading

Citations

Oct 24, 2002·Current Opinion in Hematology·J H F FalkenburgR Willemze
Jul 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alison M E WhiteleggLinda D Barber
Sep 22, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lothar HambachEls Goulmy
May 26, 2012·Blood·Miranda P DierselhuisEls Goulmy
Jun 21, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Justyna OgonekLothar Hambach
Nov 20, 2003·Bone Marrow Transplantation·S Chakrabarti, D I Marks

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