Abstract |
Human leukocyte antigen (HLA) class I antigen defects may have a negative impact on the growing application of T-cell-based immunotherapeutic strategies for treatment of leukemia. Therefore in the present study, taking advantage of a large panel of HLA class I allele-specific human monoclonal antibodies, we have compared HLA class I antigen expression on leukemic cells with that on autologous and allogeneic normal cells. Down-regulation of HLA-A and/or -B allospecificities was present in the majority of the patients studied. However, down-regulation did not affect all HLA class I alleles uniformly, but was almost exclusively restricted to HLA-A allospecificities and to HLA-B allospecificities which belong to the HLA-Bw6 group. The latter allospecificities, at variance from those that belong to the HLA-Bw4 group, do not modulate the interactions of leukemic cells with natural killer (NK) cells. Therefore, our results suggest that the selective down-regulation of HLA-A and HLA-Bw6 allospecificities associated with HLA-Bw4 preservation provides leukemic cells with an escape mechanism not only from cytotoxic T lymphocytes (CTLs), but also from NK cells. As a result T-cell-based immunotherapeutic strategies for leukemia should utilize HLA-Bw4 alloantigens as restricting elements since a selective HLA-Bw4 allele loss would provide leukemic cells with an escape mechanism from CTLs, but would increase their susceptibility to NK cell-mediated lysis.
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Authors | Christian Demanet, Arend Mulder, Veronique Deneys, Maria J Worsham, Piet Maes, Frans H Claas, Soldano Ferrone |
Journal | Blood
(Blood)
Vol. 103
Issue 8
Pg. 3122-30
(Apr 15 2004)
ISSN: 0006-4971 [Print] United States |
PMID | 15070694
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- HLA-A Antigens
- HLA-B Antigens
- HLA-Bw4 antigen
- HLA-Bw6 antigen
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Topics |
- Alleles
- Antibodies, Monoclonal
- Antibody Specificity
- Cell Line, Tumor
- Down-Regulation
- Flow Cytometry
- Gene Expression
- HLA-A Antigens
(genetics, metabolism)
- HLA-B Antigens
(genetics, metabolism)
- Humans
- Killer Cells, Natural
(immunology)
- Leukemia
(genetics, immunology)
- Mutation
- T-Lymphocytes, Cytotoxic
(immunology)
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