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Hairy Cell Leukemia

Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells

Abstract

Hairy cell leukemia (HCL) is a chronic mature B-cell leukemia characterized by malignant B cells that have typical hairy protrusions. To characterize possible HCL-associated tumor antigens, we generated an HCL-specific and HLA class II (DPw4)-restricted proliferative CD4+ T-cell clone. To identify the target antigen of these T cells, we constructed a synthetic peptide library dedicated to bind HLA DPw4, and identified a mimicry epitope recognized by the T-cell clone. With this epitope, the recognition motif of the T-cell clone was deduced and a peptide of human synaptojanin 2 (Syn 2) was identified that stimulated the HCL-reactive T-cell clone. Both Northern and Western blot analyses showed that Syn 2 expression was increased in HCL samples compared to other B cells. Besides, the Syn 2-expressing cell line AML193, with the introduced restrictive HLA-DPw4 molecules, was recognized by the HCL-specific T-cell clone. These results indicate that Syn 2 is a target of autoreactive HCL-specific T cells. Since Syn 2 is a phosphatidylinositol 4,5-biphosphatase involved in cell growth and rearrangement of actin filaments, the increased Syn 2 expression may correlate with the disease etiology or the characteristic morphologic alterations caused by the disease.

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Acknowledgements

We thank Reinout Amons and Peter van Veelen (Leiden University Medical Center) for their help with protein sequencing and mass spectrometry. We also thank Roel de Paus (Leiden University Medical Center) for his technical advice for the viral transduction studies. This work was supported by a grant from the Dutch Cancer Society.

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Spaenij-Dekking, E., Van Delft, J., Van der Meijden, E. et al. Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells. Leukemia 17, 2467–2473 (2003). https://doi.org/10.1038/sj.leu.2403174

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