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Hairy cell leukemia-specific recognition by multiple autologous HLA-DQ or DP-restricted T-cell clones
L van de Corput1, H C Kluin-Nelemans, M G Kester
1Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Researchers identified specific T-cell clones that recognize hairy cell leukemia (HCL) cells. These HCL-specific T-cells offer potential for detecting a tumor antigen in hairy cell leukemia patients.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Hairy cell leukemia (HCL) is a rare B-cell malignancy.
- The role of T-cell immunity in HCL pathogenesis is not fully understood.
- Identifying tumor-specific T-cell responses can aid in diagnostics and therapeutics.
Purpose of the Study:
- To investigate the presence and characteristics of autoreactive T cells specific to HCL cells.
- To determine if these T cells can be utilized for HCL detection.
Main Methods:
- HCL cells were activated via CD40 triggering and used to generate autologous T-cell clones.
- T-cell clone reactivity was assessed against autologous HCL cells, peripheral blood mononuclear cells (PBMC), and other cell types using a primed lymphocyte test.
- HLA restriction of T-cell recognition was analyzed through blocking and panel studies.
Main Results:
- Two types of CD4(+)BV2(+) T-cell clones and one CD4(+)BV8S3(+) T-cell clone specifically recognized autologous HCL cells.
- These T-cell clones did not react to autologous non-leukemic cells or other hematologic malignancies.
- BV2(+) T-cell recognition was restricted by HLA-DQA1*03/DQB1*0301, and BV8S3(+) T-cell recognition by DPB1*04.
Conclusions:
- Autoreactive T-cell clones with specific reactivity against HCL cells were successfully generated.
- These HCL-specific T-cell clones demonstrate potential as diagnostic tools for detecting HCL-specific tumor antigens.
Abstract:
We studied in patients with hairy cell leukemia (HCL) whether autoreactive T cells could be isolated with specific reactivity to the HCL cells. HCL cells were activated via triggering of CD40 on the cell membrane and used as stimulator cells to generate autologous T-cell clones. Two types of CD4(+)BV2(+) T-cell clones with different CDR3 rearrangements and one type of CD4(+)BV8S3(+) T-cell clone were generated from the spleen or blood. These clones specifically recognized the autologous HCL cells, without reactivity to autologous peripheral blood mononuclear cells (PBMC), phytohemagglutinin blasts, or Epstein-Barr virus-transformed B cells in a primed lymphocyte test. Blocking and panel studies using HCL cells from 11 other patients showed that recognition of the HCL cells by the BV2(+) T cells was restricted by HLA-DQA1*03/DQB1*0301, and the BV8S3(+) T cells were restricted by DPB1*04. The T-cell clones did not recognize DPB1*04(+) or DQ3(+) PBMC from healthy donors or DP/DQ matched malignant cells from patients with other hematologic malignancies, except for one patient with acute lymphoblastic leukemia. These HCL-specific T-cell clones may be used for the detection of an HCL-specific tumor antigen.
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