Identification of human telomerase reverse transcriptase-derived peptides that induce HLA-A24-restricted antileukemia cytotoxic T lymphocytes.
Human telomerase reverse transcriptase (hTERT) is considered a potential target for cancer immunotherapy because it is preferentially expressed in malignant cells. hTERT-derived peptides carrying motifs for HLA-A24 (HLA-A*2402), the most common allele among Japanese and also frequently present in persons of European descent, were examined for their capacity to elicit antileukemia cytotoxic T lymphocytes (CTLs). Two of the 5 peptides tested, VYAETKHFL and VYGFVRACL, appeared capable of generating hTERT peptide-specific and HLA-A24-restricted CTLs. The CD8(+) CTL clones specific for these hTERT peptides exerted cytotoxicity against leukemia cells in an HLA-A24-restricted manner. This cytotoxicity was inhibited by the addition of hTERT peptide-loaded autologous cells, suggesting that hTERT is naturally processed in leukemia cells and that hTERT-derived peptides are expressed on these cells and are recognized by CTLs in the context of HLA-A24. Taken together with the currently identified HLA-A2-restricted CTL epitopes derived from hTERT, identification of new CTL epitopes presented by HLA-A24 increases the feasibility of immunotherapy for leukemia using hTERT-derived peptides.
Arai
J
J
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Ehime, Japan.
Yasukawa
M
M
Ohminami
H
H
Kakimoto
M
M
Hasegawa
A
A
Fujita
S
S
D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007938:Leukemia / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012313:RNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019098:Telomerase / Q000276:immunology*
D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D010446:Peptide Fragments; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase