Augmentation of immune response by altered peptide ligands of the antigenic peptide in a human CD4+ T-cell clone reacting to TEL/AML1 fusion protein.
The 12;21 chromosomal translocation occurs in leukemic cells from 20(30% of patients with B-lineage childhood acute lymphoblastic leukemia, the result being the TEL/AML1 fusion gene carrying a sequence different from TEL or AML1. Because the protein newly formed by TEL/ AML1 fusion is probably not tolerated by human immune system, the fusion region is a good candidate for tumor antigen expressed only in TEL/ AML1-positive leukemic cells. We established two human CD4+ alphabeta T-cell clones (T31.1 and Y41.2) reacting to the TEL/AML1 fusion region, from two unrelated healthy donors. In order to do this, we stimulated peripheral blood mononuclear cells with synthetic peptides corresponding to the TEL/ AML1 fusion region. Both T31.1 and Y41.2 proliferated in response to TEL/ AML1 fusion protein as well as to a peptide IGRIAECILGMNPSR, in the context of HLA-DP5 and DP17, respectively, and killed B lymphoblastoid cells pulsed with the peptide. Furthermore, these T-cell clones proliferated in response to several altered peptide ligands carrying a single residue substitution in the TEL/AML1 peptide, and some induced augmentation of proliferation and production of Th1-type cytokines. These superagonistic altered peptide ligands can be given consideration for anti-leukemic immunotherapy.
Yun
C
C
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Senju
S
S
Fujita
H
H
Tsuji
Y
Y
Irie
A
A
Matsushita
S
S
Nishimura
Y
Y
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002999:Clone Cells; D050676:Core Binding Factor Alpha 2 Subunit; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D000276:Adjuvants, Immunologic; D050676:Core Binding Factor Alpha 2 Subunit; D008024:Ligands; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010455:Peptides; D011993:Recombinant Fusion Proteins; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein