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


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.


CONCLUSIONS
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.
Gillespie
G
G
Molecular Immunology Group, John Radcliffe Hospital, Oxford, UK.
Mutis
T
T
Schrama
E
E
Kamp
J
J
Esendam
B
B
Falkenburg
J F
JF
Goulmy
E
E
Moss
P
P
D017951:Antigen Presentation; D001704:Biopolymers; D016026:Bone Marrow Transplantation / Q000276:immunology; D002478:Cells, Cultured / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D016219:Immunotherapy, Adoptive; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D008024:Ligands; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009363:Neoplasm Proteins / Q000138:chemical synthesis / Q000276:immunology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D001704:Biopolymers; C110615:HA-1 antigen; C080145:HA-2 antigen; D008024:Ligands; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; D009842:Oligopeptides; D010446:Peptide Fragments