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The only proposed T-cell epitope derived from the TEL-AML1 translocation is not naturally processed

Item Type:Article
Title:The only proposed T-cell epitope derived from the TEL-AML1 translocation is not naturally processed
Creators Name:Popovic, J. and Li, L.P. and Kloetzel, P.M. and Leisegang, M. and Uckert, W. and Blankenstein, T.
Abstract:Adoptive therapy with T cell receptor (TCR)-engineered T cells is a promising approach in cancer treatment. While usage of T cells specific for tumor-associated antigens (TAAs) can lead to serious side effects due to autoimmunity, targeting true tumor-specific mutations, such as the products of translocations in leukemias, should reduce such a risk. A potentially ideal target might be the chimeric protein TEL-AML1, which results from the chromosomal translocation 12;21 and represents the most common fusion gene in childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL). Within the fusion region of TEL-AML1, a single epitope has been described by reverse immunology as immunogenic in HLA-A*0201 restriction settings. As a potential source of TCRs specific for this TEL-AML1 epitope, we have used mice expressing a human TCR-αβ repertoire and human major histocompatibility complex (MHC) class I. Surprisingly, we have found that, although a specific functional CD8(+) T cell response against this peptide could be evoked, the described epitope was in fact not endogenously processed. Analyses done with a potent antigen presenting cell line, as well as with purified human proteasomes, support the conclusion that this peptide cannot be proposed as a potential target in immunotherapy of ALL in HLA-A*0201-restricted fashion.
Keywords:Amino Acid Sequence, Antigen Presentation, Base Sequence, Cell Separation, Coculture Techniques, Core Binding Factor Alpha 2 Subunit, Flow Cytometry, Fusion Oncogene Proteins, Genetic Translocation, High Pressure Liquid Chromatography, Lymphocyte Activation, Molecular Sequence Data, T-Lymphocyte Epitopes, Transgenic Mice, Animals, Mice
Publisher:American Society of Hematology
Page Range:946-954
Date:28 July 2011
Official Publication:https://doi.org/10.1182/blood-2010-12-325035
PubMed:View item in PubMed

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