T cells reactive with HLA-A*0201 peptides from the histone demethylase JARID1B are found in the circulation of breast cancer patients
✍ Scribed by Julia A. Coleman; Isabel Correa; Lucienne Cooper; Hermann R. Bohnenkamp; Richard Poulsom; Joy M. Burchell; Joyce Taylor-Papadimitriou
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- French
- Weight
- 431 KB
- Volume
- 128
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
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.