CD4+ T cells from peripheral blood of a melanoma patient recognize peptides derived from nonmutated tyrosinase.
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.
Kobayashi
H
H
Department of Pathology, Asahikawa Medical College, Japan.
Kokubo
T
T
Sato
K
K
Kimura
S
S
Asano
K
K
Takahashi
H
H
Iizuka
H
H
Miyokawa
N
N
Katagiri
M
M
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*
D000951:Antigens, Neoplasm; D016207:Cytokines; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D010446:Peptide Fragments; D014442:Monophenol Monooxygenase