title: CD4+ T cells from peripheral blood of a melanoma patient recognize peptides derived from nonmutated tyrosinase.
abstract: Tyrosinase is an antigen that is expressed by normal melanocytes as well as melanoma cells, against which responses by autologous T cells have been detected. Although CD4+ T cells play an important role in tumor immunity in animal tumor models, little information about CD4+ T-cell immunity against human tumors exists. Here, we report that CD4+ T cells from the peripheral blood of a patient with melanoma respond to synthetic peptides derived from nonmutated tyrosinase. T-cell clones were generated that recognized the tyrosinase p386-406 peptide when it was presented by the HLA-DR15 (DRB1*1501) molecule. The CD4+ T-cell clone also recognized autologous EBV-transformed B-lymphoblastoid cell lines that had been pulsed with the lysate of melanoma cells. The synthetic tyrosinase p386-406 peptide was capable of binding to HLA-DR15 (DRB1*1501) molecules on cell surface of DR15 homozygous cells. Thus, the finding that nonmutated tyrosinase peptides are immunogenic in a melanoma patient may provide the basis for the development of cancer immunotherapy, based on knowledge of synthetic tumor-associated peptide antigens.
authors.affiliation: Department of Pathology, Asahikawa Medical College, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Kokubo
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Asano
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Iizuka
authors.forename: N
authors.initials: N
authors.lastname: Miyokawa
authors.forename: M
authors.initials: M
authors.lastname: Katagiri
mesh_terms: D000938:Antigen-Presenting Cells; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002461:Cell Line, Transformed; D002474:Cell-Free System / Q000187:drug effects; D002999:Clone Cells; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D059810:HLA-DR Serological Subtypes; D004854:Herpesvirus 4, Human; D006801:Humans; D008545:Melanoma / Q000097:blood*; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D012878:Skin Neoplasms / Q000097:blood*
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D010446:Peptide Fragments; D014442:Monophenol Monooxygenase