A decapeptide (Gln-Asp-Leu-Thr-Met-Lys-Tyr-Gln-Ile-Phe) from human melanoma is recognized by CTL in melanoma patients.
The decapeptide 810 (QDLTMKYQIF) contains the antigenic epitope (KYQI) recognized by human mAb L92. This sequence is found in a 43-kDa protein associated with human melanoma M14. We examined the expression of 810 in human cells and its involvement in the cellular immune responses of melanoma patients. Nineteen stage III melanoma patients and 19 normal donors were studied for their responses to 810. All patients were immunized in vivo with an allogeneic melanoma cell vaccine. PBMC cytotoxicity was tested on autologous EBV-transformed B lymphoblastoid cell lines (BCL) pulsed with 810 and autologous melanomas. Proliferative responses of PBMC to 810 were evaluated by using [3H]Tdr incorporation assays. Western blotting revealed that the 43-kDa protein was not specific to melanoma but was common to various cells. However, the percentage of cytotoxicity of PBMC against autologous 810-pulsed BCL was significantly greater in melanoma patients than in normal controls (p < 0.005). Cytotoxicity was increased after melanoma cell vaccine immunization in 15 patients (78%). Proliferative responses to 810 were observed only in melanoma patients and were enhanced in 12 patients (63%) after vaccination. Restimulation of PBMC from vaccinated patients with 810 increased cytotoxicity against both autologous 810-pulsed BCL and melanomas. These targets were lysed by CD8+ T lymphocytes in an HLA class I-restricted manner. HLA-A2 and -A11 seemed to serve as the 810-presenting molecule. Our findings indicate that 810 may function as an epitope for CTL on human melanoma and can be used as a vaccine.
Morioka
N
N
John Wayne Cancer Institute, Santa Monica, CA 90404.
Kikumoto
Y
Y
Hoon
D S
DS
Morton
D L
DL
Irie
R F
RF
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000951:Antigens, Neoplasm; D000939:Epitopes; D006680:HLA Antigens; D009842:Oligopeptides; C090853:decapeptide 810