Identification of two novel tumor-associated antigens recognized by HLA-B46-restricted cytotoxic T lymphocytes.
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.
Shichijo
Shigeki
S
Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. shichijo@med.kurume-u.ac.jp
Azuma
Kohichi
K
Komatsu
Nobukazu
N
Kawamoto
Naoki
N
Takedatsu
Hiroko
H
Shomura
Hiroki
H
Sawamizu
Hiromi
H
Maeda
Yoshiaki
Y
Ito
Masaaki
M
Itoh
Kyogo
K
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018076:DNA, Complementary; D000939:Epitopes / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D011755:Pyrophosphatases / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097630:Inosine Triphosphatase
D018076:DNA, Complementary; D000939:Epitopes; D015235:HLA-B Antigens; D009687:Nuclear Proteins; D011755:Pyrophosphatases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D000097630:Inosine Triphosphatase; C080311:HLA-B46 antigen