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 prote in associated with human melanoma M14. We examined the expression of 8 10 in human cells and its involvement in the cellular immune responses of melanoma patients. Nineteen stage III melanoma patients and 19 nor mal donors were studied for their responses to 810. All patients were immunized in vivo with an allogeneic melanoma cell vaccine. PBMC cytot oxicity was tested on autologous EBV-transformed B lymphoblastoid cell lines (BCL) pulsed with 810 and autologous melanomas. Proliferative r esponses of PBMC to 810 were evaluated by using [H-3]Tdr incorporation assays. Western blotting revealed that the 43-kDa protein was not spe cific to melanoma but was common to various cells. However, the percen tage of cytotoxicity of PBMC against autologous 810-pulsed BCL was sig nificantly greater in melanoma patients than in normal controls (p < 0 .005). Cytotoxicity was increased after melanoma cell vaccine immuniza tion in 15 patients (78%). Proliferative responses to 810 were observe d only in melanoma patients and were enhanced in 12 patients (63%) aft er vaccination. Restimulation of PBMC from vaccinated patients with 81 0 increased cytotoxicity against both autologous 810-pulsed BCL and me lanomas. These targets were lysed by CD8(+) T lymphocytes in an HLA cl ass I-restricted manner. HLA-A2 and -A11 seemed to serve as the 810-pr esenting molecule. Our findings indicate that 810 may function as an e pitope for CTL on human melanoma and can be used as a vaccine.