Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.
Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > 25% of ALL-patients. In this study, we have examined whether the chimeric ETV6-AML1 protein could serve as a tumor specific antigen for CTL in HLA-A2.1 individuals. We have identified a nonapeptide (RIAECILGM), encoded by the fusion region of the ETV6-AML1 protein, that binds to HLA-A2.1 molecules and induces specific primary CTL in peripheral blood lymphocytes from healthy donors. These CTL specifically lysed HLA-A2.1 tumor cells endogeneously expressing the ETV6-AML fusion protein. CTL with similar functional capacities were found with high frequencies and cloned from one patient's bone marrow indicating that ETV6-AML1-specific anti-ALL CTL are, at least in some patients, spontaneously stimulated and might participate to host antileukemia defense.
Immunologie Cellulaire Anti-Virale, Institut Pasteur 75015 Paris Cedex 15, France.
P
P
Yotnda
F
F
Garcia
M
M
Peuchmaur
B
B
Grandchamp
M
M
Duval
F
F
Lemonnier
E
E
Vilmer
P
P
Langlade-Demoyen
D000595:Amino Acid Sequence; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D015514:Oncogene Proteins, Fusion; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010455:Peptides; D011993:Recombinant Fusion Proteins; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein