HLA-DRB1*16-restricted recognition of myeloid cells, including CD34+ CML progenitor cells.
The therapeutic effect of a human leucocyte antigen (HLA)-identical allogeneic stem cell transplantation (allo-SCT) for the treatment of haematological malignancies is mediated partly by the allogeneic T cells that are administered together with the stem cell graft. Chronic myeloid leukaemia (CML) is particularly sensitive to this graft-versus-leukaemia (GVL) effect. Several studies have shown that in allogeneic responses both CD4 and CD8 cells are capable of strong antigen-specific growth inhibition of leukaemic progenitor cells, but that CD4 cells mainly exert the GVL effect against CML. Efficient activation of allogeneic CD4 cells, as well as CD8 cells, may explain the sensitivity of CML cells to elimination by allogeneic T cells. Identification of the antigens recognized by CD4 cells is crucial in understanding the mechanism through which CML cells are so successful in activating allogeneic T cells. In the present report, we describe the characterization of an allogeneic CD4 T-cell clone, DDII.4.4. This clone was found to react against an antigen that is specifically expressed in myeloid cells, including CD34+ CML cells. The antigen recognition is restricted by HLA-DRB1*16. To our knowledge, this is only the second report on an allogeneic CD4 T-cell clone that reacts with early CD34+ myeloid progenitor cells.
Ebeling
Saskia B
SB
Jordan Laboratory for Haemato-Oncology, Department of Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands. s.ebeling@azu.nl
Ivanov
Roman
R
Hol
Samantha
S
Aarts
Tineke I
TI
Hagenbeek
Anton
A
Verdonck
Leo F
LF
Petersen
Eefke J
EJ
D000595:Amino Acid Sequence; D018952:Antigens, CD34; D001483:Base Sequence; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains