1. Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells
- Author
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Jan W. Drijfhout, Johanna Kluin-Nelemans, E.H.A. Spaenij-Dekking, Jhf Falkenburg, Hoebert S. Hiemstra, Frits Koning, J. L. Van Delft, E. van der Meijden, Faculteit Medische Wetenschappen/UMCG, Damage and Repair in Cancer Development and Cancer Treatment - 1, and Stem Cell Aging Leukemia and Lymphoma
- Subjects
CD4-Positive T-Lymphocytes ,Phosphatidylinositol 4,5-Diphosphate ,Cancer Research ,Chronic lymphocytic leukemia ,Epitopes, T-Lymphocyte ,BINDING CHARACTERISTICS ,Nerve Tissue Proteins ,Human leukocyte antigen ,Synaptojanin ,Biology ,Epitope ,peptide library ,Antigen ,Transduction, Genetic ,MIMICRY EPITOPES ,medicine ,Humans ,hairy cell leukemia ,Hairy cell leukemia ,Cloning, Molecular ,synaptojanin 2 ,CD4T cell epitope ,Leukemia, Hairy Cell ,IDENTIFICATION ,RECEPTOR ,Gene Expression Regulation, Leukemic ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,SYNTHETIC PEPTIDE LIBRARIES ,Histocompatibility Antigens Class II ,U937 Cells ,Hematology ,medicine.disease ,CLATHRIN-MEDIATED ENDOCYTOSIS ,Virology ,Molecular biology ,Phosphoric Monoester Hydrolases ,Leukemia ,Retroviridae ,Oncology ,TUBULORETICULAR INCLUSIONS ,Cell culture ,VIRAL PARTICLES ,K562 Cells ,DISEASE-ASSOCIATED DQ(ALPHA-1-ASTERISK-0501 ,HeLa 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.
- Published
- 2003