title: Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs.
abstract: Here, we describe an human leukocyte antigen (HLA)-A*24:02-restricted cytotoxic T-lymphocyte (CTL) clone, 1G3, established from naïve CD8(+) T-lymphocytes obtained from a healthy donor stimulated with HLA-modified TOV21G, an ovarian cancer cell line. The 1G3 clone responds not only to ovarian cancer cells in the context of HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive T-cell receptor recognition. Expression screening using a complementary DNA library constructed from TOV21G messenger RNA revealed that this alloreactivity was mediated through the nine-mer peptide VRTPYTMSY, derived from RNA-binding motif protein 4. To our knowledge, this study presents the first example of the allorecognition of an HLA-Cw molecule by HLA-A-restricted T-cells, thereby revealing a naturally processed epitope peptide. These findings provide the structural bases for the allorecognition of human T-cells. In addition, this study suggests that unexpected alloresponses occur in certain HLA combinations, and further study is needed to understand the mechanisms of alloreactivity for better prediction of alloresponses in clinical settings.
authors.affiliation: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.|Department of Gynecology, Graduate School of Medicine, Nagoya, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Yamada
authors.affiliation: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Demachi-Okamura
authors.affiliation: Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.|Department of Hematology & Oncology, Fujita Health University, Toyoake, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Akatsuka
authors.affiliation: Department of Gynecology, Graduate School of Medicine, Nagoya, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Gynecology, Graduate School of Medicine, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Gynecology, Graduate School of Medicine, Nagoya, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Kikkawa
authors.affiliation: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.|Department of Cellular Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuzushima
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002999:Clone Cells; D003429:Cross Reactions / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D059871:HLA-A24 Antigen / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018076:DNA, Complementary; D000939:Epitopes; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D015236:HLA-C Antigens; C040178:HLA-C*70 antigen; D010455:Peptides; D016601:RNA-Binding Proteins
keywords: HLA-A*24:02; HLA-Cw*07:02; alloreactivity; antigen-presenting cells; cytotoxic T-lymphocyte; ovarian cancer