Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes.
Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-related protein-1 (gp75) were evaluated for recognition by HLA-A2-restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.
Kawakami
Y
Y
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Eliyahu
S
S
Sakaguchi
K
K
Robbins
P F
PF
Rivoltini
L
L
Yannelli
J R
JR
Appella
E
E
Rosenberg
S A
SA
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000032:analysis*; D000939:Epitopes / Q000032:analysis; D015789:HLA-A2 Antigen / Q000502:physiology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology
D000951:Antigens, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins