title: Identification of promiscuous HLA-DR-restricted CD4⁺ T-cell epitopes on the cancer-testis antigen HCA587.
abstract: The cancer testis antigen HCA587 is an attractive candidate for T cell-based immunotherapy because it is overexpressed in a wide spectrum of malignant tumors but not normal tissues, except testis. Several CTL epitopes derived from HCA587 have been described. Our aim was to identify helper T lymphocyte epitopes of HCA587 for the optimization of T cell-based immunotherapies against HCA587-expressing tumors. Candidate helper T lymphocyte epitopes for HCA587 were predicted using the SYFPEITHI algorithm and were tested for their ability to induce helper T lymphocyte responses by in vitro peptide vaccination of CD4(+) T lymphocytes from healthy individuals and hepatocellular carcinoma patients. Four CD4(+) T-cell epitopes for HCA587 (p43-57, p145-159, p186-200 and p249-263) were identified. Among them, the p43-57 epitope was shown to be naturally processed and presented by HCA587-expressing tumor cells as well as autologous dendritic cells pulsed with whole-protein HCA587. Notably, this epitope behaved as a promiscuous T-cell epitope as it stimulated T cells in the context of more than one HLA class II allele. Thus, p43-57 is the first HCA587-derived major histocompatibility complex class II-restricted epitope to fulfil all prerequisites for use as a peptide vaccine in patients with HCA587-expressing tumors.
authors: Department of Immunology, Peking University Health Science Center, Beijing, China.
authors: Weigang
authors: W
authors: Wen
authors: Lijie
authors: L
authors: Zhang
authors: Jirun
authors: J
authors: Peng
authors: Juanjuan
authors: J
authors: Chen
authors: Jiaqing
authors: J
authors: Hao
authors: Xiaofeng
authors: X
authors: Li
authors: Xiaoping
authors: X
authors: Qian
authors: Pumei
authors: P
authors: Zeng
authors: Yu
authors: Y
authors: Zhang
authors: Yanhui
authors: Y
authors: Yin