RRC ID 45024
Author Tomita Y, Yuno A, Tsukamoto H, Senju S, Yoshimura S, Osawa R, Kuroda Y, Hirayama M, Irie A, Hamada A, Jono H, Yoshida K, Tsunoda T, Kohrogi H, Yoshitake Y, Nakamura Y, Shinohara M, Nishimura Y.
Title Identification of CDCA1-derived long peptides bearing both CD4+ and CD8+ T-cell epitopes: CDCA1-specific CD4+ T-cell immunity in cancer patients.
Journal Int J Cancer
Abstract We recently identified a novel cancer-testis antigen, cell division cycle associated 1 (CDCA1) using genome-wide cDNA microarray analysis, and CDCA1-derived cytotoxic T lymphocyte (CTL)-epitopes. In this study, we attempted to identify CDCA1-derived long peptides (LPs) that induce both CD4+ helper T (Th) cells and CTLs. We combined information from a recently developed computer algorithm predicting HLA class II-binding peptides with CDCA1-derived CTL-epitope sequences presented by HLA-A2 (A*02:01) or HLA-A24 (A*24:02) to select candidate CDCA1-LPs encompassing both Th cell epitopes and CTL-epitopes. We studied the immunogenicity of CDCA1-LPs and the cross-priming potential of LPs bearing CTL-epitopes in both human in vitro and HLA-class I transgenic mice in vivo. Then we analyzed the Th cell response to CDCA1 in head-and-neck cancer (HNC) patients before and after vaccination with a CDCA1-derived CTL-epitope peptide using IFN-γ enzyme-linked immunospot assays. We identified two CDCA1-LPs, CDCA1(39–64)-LP and CDCA1(55–78)-LP, which encompass naturally processed epitopes recognized by Th cells and CTLs. CDCA1-specific CTLs were induced through cross-presentation of CDCA1-LPs in vitro and in vivo. In addition, CDCA1-specific Th cells enhanced induction of CDCA1-specific CTLs. Furthermore, significant frequencies of CDCA1-specific Th cell responses were detected after short-term in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with CDCA1-LPs in HNC patients (CDCA1(39–64)-LP, 74%; CDCA1(55–78)-LP, 68%), but not in healthy donors. These are the first results demonstrating the presence of CDCA1-specific Th cell responses in HNC patients and underline the possible utility of CDCA1-LPs for propagation of both CDCA1-specific Th cells and CTLs.
Volume 134(2)
Pages 352-66
Published 2014-1-15
DOI 10.1002/ijc.28376
PMID 24734272
MeSH Animals CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / metabolism CD4-Positive T-Lymphocytes / pathology CD8-Positive T-Lymphocytes / immunology* CD8-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / pathology Case-Control Studies Cell Cycle Proteins / immunology* Cell Cycle Proteins / metabolism Cells, Cultured Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic Fibroblasts / immunology Fibroblasts / metabolism Fibroblasts / pathology Flow Cytometry HLA Antigens / immunology HLA Antigens / metabolism Head and Neck Neoplasms / immunology* Head and Neck Neoplasms / metabolism Head and Neck Neoplasms / pathology Humans Mice Neoplasm Metastasis Neoplasm Recurrence, Local / immunology* Neoplasm Recurrence, Local / metabolism Neoplasm Recurrence, Local / pathology Peptide Fragments / immunology* Peptide Fragments / metabolism Platelet Membrane Glycoprotein IIb / immunology* Platelet Membrane Glycoprotein IIb / metabolism Recombinant Proteins / immunology Recombinant Proteins / metabolism Th1 Cells / immunology Th1 Cells / metabolism Th1 Cells / pathology
IF 5.145
Times Cited 18
Human and Animal Cells T2(RCB1932)