Identification of novel human leukocyte antigen‐A*11:01‐restricted cytotoxic T‐lymphocyte epitopes derived from osteosarcoma antigen papillomavirus binding factor. Issue 4 (12th March 2019)

• Record Type: Journal Article
• Authors: Li, Dongliang; Toji, Shingo; Watanabe, Kazue; Torigoe, Toshihiko; Tsukahara, Tomohide
• Is Part Of: Cancer science. Volume 110:Issue 4(2019)
• Page Start: 1156
• Page End: 1168
• Publication Date: 2019-03-12
• Subjects: CTL epitope -- in vitro folding ability -- MHC‐tetramer -- osteosarcoma -- PBF; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13973
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Osteosarcoma is the most common malignancy of bone that affects young people. Neoadjuvant chemotherapy and surgery have significantly improved the prognosis. However, the prognosis of non‐responders to chemotherapy is still poor. To develop peptide‐based immunotherapy for osteosarcoma, we previously identified CTL epitopes derived from papillomavirus binding factor (PBF) in the context of human leukocyte antigen (HLA)‐A2, HLA‐A24 and HLA‐B55. In the present study, we identified two novel CTL epitopes, QVT (QVTVWLLEQK) and LSA (LSALPPPLHK), in the context of HLA‐A11 using a sequence of screenings based on the predicted affinity of peptides, in vitro folding ability of peptide/HLA‐A11 complex, reactivity of peptide/HLA‐A11 tetramer and interferon (IFN)‐γ production of T cells that was induced by mixed lymphocyte peptide culture under a limiting dilution condition. CTL clones directed to QVT and LSA peptides showed specific cytotoxicity against HLA‐A11 + PBF + osteosarcoma (HOS‐A11) cells. In contrast, another epitope, ASV (ASVLSRRLGK), could highly induce cognate tetramer‐positive CTL. This might be because the ASV peptide mimics the peptide ASV (R6Q) (ASVLSQ RLGK) derived from bacterial polypeptides, ROK family proteins. However, ASV‐induced CTL did not show cytokine production against the cognate peptide. In conclusion, the CTL epitopes QVT and LSA peptides might be useful for the development of immunotherapy targeting PBF for patients with osteosarcoma. Abstract : We identified two novel CTL epitopes derived from osteosarcoma antigen PBF in the context of HLA‐A11 using a sequence of screenings based on the predicted affinity of peptides, in vitro folding ability of peptide/HLA‐A11 complex, reactivity of MHC‐tetramer and IFN‐γ production of T cells that were induced by mixed lymphocyte peptide culture under limiting dilution conditions.