Identification of an HLA-A2-restricted epitope peptide derived from hypoxia-inducible protein 2 (HIG2).

Abstract

We herein report the identification of an HLA-A2 supertype-restricted epitope peptide derived from hypoxia-inducible protein 2 (HIG2), which is known to be a diagnostic marker and a potential therapeutic target for renal cell carcinoma. Among several candidate peptides predicted by the HLA-binding prediction algorithm, HIG2-9-4 peptide (VLNLYLLGV) was able to effectively induce peptide-specific cytotoxic T lymphocytes (CTLs). The established HIG2-9-4 peptide-specific CTL clone produced interferon-γ (IFN-γ) in response to HIG2-9-4 peptide-pulsed HLA-A*02:01-positive cells, as well as to cells in which HLA-A*02:01 and HIG2 were exogenously introduced. Moreover, the HIG2-9-4 peptide-specific CTL clone exerted cytotoxic activity against HIG2-expressing HLA-A*02:01-positive renal cancer cells, thus suggesting that the HIG2-9-4 peptide is naturally presented on HLA-A*02:01 of HIG-2-expressing cancer cells and is recognized by CTLs. Furthermore, we found that the HIG2-9-4 peptide could also induce CTLs under HLA-A*02:06 restriction. Taken together, these findings indicate that the HIG2-9-4 peptide is a novel HLA-A2 supertype-restricted epitope peptide that could be useful for peptide-based immunotherapy against cancer cells with HIG2 expression.

• Authors: Sachiko Yoshimura, Takuya Tsunoda, Ryuji Osawa, Makiko Harada, Tomohisa Watanabe, Tetsuro Hikichi, Masahiro Katsuda, Motoki Miyazawa, Masaji Tani, Makoto Iwahashi, Kazuyoshi Takeda, Toyomasa Katagiri, Yusuke Nakamura, Hiroki Yamaue
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e85267 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24416375 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• Epitopes
• HILPDA protein, human
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Neoplasm Proteins
• Peptides
• Interferon-gamma

Topics

• Amino Acid Sequence
• Antigens, Neoplasm (chemistry, genetics, immunology)
• Carcinoma, Renal Cell (genetics, immunology, pathology)
• Cell Line, Tumor
• Epitopes (chemistry, genetics, immunology)
• Gene Expression (immunology)
• HLA-A2 Antigen (chemistry, genetics, immunology)
• Humans
• Interferon-gamma (biosynthesis, immunology)
• Kidney Neoplasms (genetics, immunology, pathology)
• Lymphocyte Activation (drug effects)
• Molecular Sequence Data
• Neoplasm Proteins (chemistry, genetics, immunology)
• Peptides (chemistry, genetics, immunology, pharmacology)
• Protein Binding
• T-Lymphocytes, Cytotoxic (cytology, drug effects, immunology)