Identification of an immunogenic HLA-A*0201-binding T-cell epitope of the transcription factor PAX2
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Identification of an immunogenic HLA-A*0201-binding T-cell epitope of the transcription factor PAX2. / Asemissen, Anne Marie; Haase, Doreen; Stevanovic, Stefan; Bauer, Sandra; Busse, Antonia; Thiel, Eckhard; Rammensee, Hans-Georg; Keilholz, Ulrich; Scheibenbogen, Carmen.
in: J IMMUNOTHER, Jahrgang 32, Nr. 4, 05.2009, S. 370-5.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Identification of an immunogenic HLA-A*0201-binding T-cell epitope of the transcription factor PAX2
AU - Asemissen, Anne Marie
AU - Haase, Doreen
AU - Stevanovic, Stefan
AU - Bauer, Sandra
AU - Busse, Antonia
AU - Thiel, Eckhard
AU - Rammensee, Hans-Georg
AU - Keilholz, Ulrich
AU - Scheibenbogen, Carmen
PY - 2009/5
Y1 - 2009/5
N2 - PAX2 is a transcription factor and member of the highly conserved family of paired box genes. PAX2 is aberrantly expressed in a variety of solid and hematologic malignancies. PAX2 regulates the transcription factor Wilms tumor gene 1, which is a promising target of cancer immunotherapy. The aim of this study was to apply a modified reverse immunology strategy to identify immunogenic epitopes of PAX2 which could be useful for cancer immunotherapy. Thirteen potential HLA-A*0201 epitopes were predicted by a major histocompatibility complex binding algorithm (SYFPEITHI) and a proteasome cleavage algorithm (PAProC) and screened for recognition by T cells from HLA-A*02-positive cancer patients using intracellular cytokine cytometry. Epitope-specific T cells were generated from CD4CD25 regulatory T-cell-depleted peripheral blood mononuclear cell. Nine of 20 colorectal cancer patients, 1 of 13 renal cell carcinoma patients, and 2 of 17 lymphoma patients had a spontaneous CD8 T-cell response toward at least 1 of 6 PAX2 peptide pools. None of the 20 healthy subjects showed reactivity toward PAX2. PAX2.337-345 (TLPGYPPHV)-specific T cells could repeatedly be generated, which specifically lysed the PAX2 expressing colorectal tumor cell line SW480. In this study, a modified reverse immunology strategy was employed to identify a first immunogenic HLA-A*0201 restricted T-cell epitope and natural ligand of the tumor antigen PAX2. Thus, PAX2 is another embryonic transcription factor, which is of potential interest as immunotherapy target antigen.
AB - PAX2 is a transcription factor and member of the highly conserved family of paired box genes. PAX2 is aberrantly expressed in a variety of solid and hematologic malignancies. PAX2 regulates the transcription factor Wilms tumor gene 1, which is a promising target of cancer immunotherapy. The aim of this study was to apply a modified reverse immunology strategy to identify immunogenic epitopes of PAX2 which could be useful for cancer immunotherapy. Thirteen potential HLA-A*0201 epitopes were predicted by a major histocompatibility complex binding algorithm (SYFPEITHI) and a proteasome cleavage algorithm (PAProC) and screened for recognition by T cells from HLA-A*02-positive cancer patients using intracellular cytokine cytometry. Epitope-specific T cells were generated from CD4CD25 regulatory T-cell-depleted peripheral blood mononuclear cell. Nine of 20 colorectal cancer patients, 1 of 13 renal cell carcinoma patients, and 2 of 17 lymphoma patients had a spontaneous CD8 T-cell response toward at least 1 of 6 PAX2 peptide pools. None of the 20 healthy subjects showed reactivity toward PAX2. PAX2.337-345 (TLPGYPPHV)-specific T cells could repeatedly be generated, which specifically lysed the PAX2 expressing colorectal tumor cell line SW480. In this study, a modified reverse immunology strategy was employed to identify a first immunogenic HLA-A*0201 restricted T-cell epitope and natural ligand of the tumor antigen PAX2. Thus, PAX2 is another embryonic transcription factor, which is of potential interest as immunotherapy target antigen.
KW - Algorithms
KW - Amino Acid Sequence
KW - CD8-Positive T-Lymphocytes/immunology
KW - Carcinoma, Renal Cell/immunology
KW - Cell Line, Tumor
KW - Colorectal Neoplasms/immunology
KW - Epitopes, T-Lymphocyte/immunology
KW - HLA-A Antigens/immunology
KW - HLA-A2 Antigen
KW - Humans
KW - Lymphoma/immunology
KW - Molecular Sequence Data
KW - Nuclear Proteins/genetics
KW - PAX2 Transcription Factor/immunology
KW - Peptides/immunology
U2 - 10.1097/CJI.0b013e31819d4e09
DO - 10.1097/CJI.0b013e31819d4e09
M3 - SCORING: Journal article
C2 - 19342968
VL - 32
SP - 370
EP - 375
JO - J IMMUNOTHER
JF - J IMMUNOTHER
SN - 1524-9557
IS - 4
ER -