Hematopoietic lineage-restricted minor histocompatibility antigen HA-1 in graft-versus-leukemia activity after donor lymphocyte infusion.
Immunocompetent alloreactive donor lymphocytes directed against minor histocompatibility antigens are supposed to be responsible for graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity after allogeneic stem cell transplantation. The authors describe the detection of HA-1-specific T cells by peptide-loaded dimers and flow cytometry in the peripheral blood of a patient in complete remission but without GvHD after donor lymphocyte infusion for chemotherapy-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia. The HA-1-specific T cells were sorted and an alloreactive, polyclonal T-cell line with specific lytic activity against HA-1-positive target cells, including leukemic cells, was established. Although P190 bcr/abl peptide-specific CD8positive T cells were detected in the peripheral blood at the same time, these T cells could not be expanded. Furthermore, no P190 bcr/abl peptide-specific T-cell response could be induced in vitro, even when peptide-loaded dendritic cells were used as stimulator cells. The authors conclude that in the absence of GvHD, HA-1-specific rather than P190 bcr/abl-specific T cells are responsible for ongoing GvL activity.
Kircher
Brigitte
B
Laboratory for Tumor and Immunobiology, Bone Marrow Transplant Unit, Division of Hematology & Oncology, Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, Austria. brigitte.kircher@uklibk.ac.at
Wolf
Maria
M
Stevanovic
Stefan
S
Rammensee
Hans-Georg
HG
Grubeck-Loebenstein
Beatrix
B
Gastl
Günther
G
Nachbaur
David
D
D002455:Cell Division; D019070:Cell Lineage; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000166:cytology; D019281:Dimerization; D005434:Flow Cytometry; D020544:Graft vs Leukemia Effect; D015234:HLA-A Antigens / Q000737:chemistry*; D015789:HLA-A2 Antigen; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007938:Leukemia / Q000628:therapy*; D008214:Lymphocytes / Q000166:cytology*; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D011485:Protein Binding; D013601:T-Lymphocytes / Q000378:metabolism
C110615:HA-1 antigen; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D010455:Peptides