Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells.
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.
Spaenij-Dekking
E H A
EH
Department of Hematology, Leiden University Medical Center, The Netherlands.
Van Delft
J
J
Van Der Meijden
E
E
Hiemstra
H S
HS
Falkenburg
J H F
JH
Koning
F
F
Drijfhout
J W
JW
Kluin-Nelemans
J C
JC
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003001:Cloning, Molecular; D018984:Epitopes, T-Lymphocyte; D015973:Gene Expression Regulation, Leukemic; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D020014:K562 Cells; D007943:Leukemia, Hairy Cell / Q000276:immunology* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology*; D019151:Peptide Library; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D020298:U937 Cells
D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D009419:Nerve Tissue Proteins; D019151:Peptide Library; D019269:Phosphatidylinositol 4,5-Diphosphate; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases