Identification of a new HLA-A*0201-restricted CD8+ T cell epitope from hepatocellular carcinoma-associated antigen HCA587.

Abstract

For the development of peptide-based cancer immunotherapies, we aimed to identify specific HLA-A*0201-restricted CTL epitopes in hepatocellular carcinoma (HCC) associated antigen HCA587, which has been identified as a member of the cancer/testis (CT) antigens highly expressed in HCC. We first combined the use of an HLA-A*0201/peptide binding algorithm and T2 binding assays with the induction of specific CD8(+) T cell lines from normal donors by in vitro priming with high-affinity peptides, then IFN-gamma release and cytotoxicity assays were employed to identify the specific HLA-A*0201 CD8(+) T cell epitope using peptide-loaded T2 cells or the HCA587 protein(+) HCC cell line HepG2. In the six candidate synthesized peptides, two peptides showed higher binding ability in T2 binding assays. No. 2 peptide, encompassing amino acid residues FLAKLNNTV (HCA587(317-325)), was able to activate a HCA587-specific CD8(+) T-cell response in human lymphocyte cultures from two normal donors and two HCC patients, and these HCA587-specific CD8(+) T cells recognized peptide-pulsed T2 cells as well as the HCA587 protein(+) HCC cell line HepG2 in IFN-gamma release and cytotoxicity assays. The results indicate that no. 2 peptide is a new HLA-A*0201-restricted CTL epitope capable of inducing HCA587-specific CTLs. Our data suggest that identification of this new HCA587/HLA-A*0201 peptide FLAKLNNTV may facilitate the design of peptide-based immunotherapies for the treatment of HCA587-bearing HCC patients.

• Authors: B Li, Y Wang, J Chen, H Wu, W Chen
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 140 Issue 2 Pg. 310-9 (May 2005) ISSN: 0009-9104 [Print] England
• PMID: 15807856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• MAGEC2 protein, human
• Neoplasm Proteins
• RNA, Messenger

Topics

• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Hepatocellular (immunology)
• Cytotoxicity, Immunologic
• Epitopes, T-Lymphocyte (immunology)
• Gene Expression (immunology)
• HLA-A Antigens (immunology)
• HLA-A2 Antigen
• Humans
• Liver Neoplasms (immunology)
• Neoplasm Proteins (genetics, immunology, metabolism)
• RNA, Messenger (genetics)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured