Identification of two novel tumor-associated antigens recognized by HLA-B46-restricted cytotoxic T lymphocytes.

Abstract

The objective of this study was to identify novel genes and peptides capable of inducing tumor-reactive cytotoxic T lymphocytes (CTLs) in cancer patients with an HLA-B46 allele, which is preferentially expressed in Asians. We show that two genes encoding splicing factor (SF) 2 and inosine triphosphate pyrophosphatase (ITPA) have epitopes recognized by HLA-B46-restricted and tumor cell-reactive CTL lines established from tumor-infiltrating lymphocytes of colon cancer. The SF2 is essential for constitutive pre-mRNA splicing, while the enzyme ITPA controls nucleotide levels. The mRNA expression levels of these genes were higher in tumor cells than those in normal tissues. Five peptides, three from SF2 and two from ITPA, had the ability to induce HLA-B46-restricted and peptide-specific CTLs reactive to tumor cells in peripheral blood mononuclear cells of cancer patients. These results may provide new information for better understanding of host-tumor interaction at the molecular level and the development of peptide-based immunotherapy for HLA-B46+ cancer patients.

• Authors: Shigeki Shichijo, Kohichi Azuma, Nobukazu Komatsu, Naoki Kawamoto, Hiroko Takedatsu, Hiroki Shomura, Hiromi Sawamizu, Yoshiaki Maeda, Masaaki Ito, Kyogo Itoh
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 12 Issue 6 Pg. 895-902 (Dec 2003) ISSN: 1107-3756 [Print] Greece
• PMID: 14612963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Epitopes
• HLA-B Antigens
• HLA-B46 antigen
• Nuclear Proteins
• RNA, Messenger
• RNA-Binding Proteins
• Serine-Arginine Splicing Factors
• Pyrophosphatases
• inosine triphosphatase

Topics

• Animals
• COS Cells
• Chlorocebus aethiops
• DNA, Complementary
• Epitopes (immunology)
• HLA-B Antigens (immunology)
• Humans
• Nuclear Proteins (genetics, immunology)
• Pyrophosphatases (genetics, immunology)
• RNA, Messenger (metabolism)
• RNA-Binding Proteins
• Serine-Arginine Splicing Factors
• T-Lymphocytes, Cytotoxic (immunology)