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T cells reactive with HLA‐A*0201 peptides from the histone demethylase JARID1B are found in the circulation of breast cancer patients
Author(s) -
Coleman Julia A.,
Correa Isabel,
Cooper Lucienne,
Bohnenkamp Hermann R.,
Poulsom Richard,
Burchell Joy M.,
TaylorPapadimitriou Joyce
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25792
Subject(s) - cytotoxic t cell , cd8 , cancer research , breast cancer , microbiology and biotechnology , t cell , biology , antigen , cancer , ctl* , immunology , in vitro , immune system , biochemistry , genetics
The nuclear protein PLU‐1/JARID1B/KDM5 is widely expressed in breast cancers while showing highly restricted expression in normal adult tissues. To investigate whether JARID1B is a potential target antigen for immunotherapy of breast cancer, we have analyzed the responses of CD8 + T cells to JARID1B HLA‐A*0201 peptides in vitro and used peptide multimers to detect the presence of JARID1B reactive T cells in the circulation of breast cancer patients. Peptides were selected using two web‐based algorithms: criteria for inclusion being a high score in both prediction algorithms, and nonhomology with retinoblastoma binding protein‐2 (RBP2/JARID1A/KDM5A). A 65‐peptide panel was selected and assayed for binding strength by competition assay to obtain the IC 50 . The immunogenicity in vitro of these peptides was assessed by T cell stimulation experiments, using autologous dendritic cells as APCs in the first rounds followed by autologous lymphoblasts. Fourteen of the peptides assayed produced cultures having >2% of the CD8 + cells being IFN‐γ + after 3–6 rounds of stimulation. An HLA‐A*0201 cell line could activate the specific T cells if pulsed with peptide, but endogenous peptide levels were insufficient for activation. Nevertheless, multimer staining of circulating T cells from breast cancer patients showed a significantly higher percentage of multimer positive CD8 + T cells, as compared to healthy adults for two of three JARID1B epitopes tested. One of these, peptide 73 (QLYALPCVL), was analyzed for memory phenotype, and found to have a significantly higher proportion of central memory T cells than the control group, demonstrating a previous exposure to the peptide.