Identification of a novel peptide derived from the melanocyte-specific gp100 antigen as the dominant epitope recognized by an HLA-A2.1-restricted anti-melanoma CTL line.
Cytotoxic T lymphocytes (CTL) reactive with human melanoma tumor cells occasionally display cross-reactivity with normal melanocytes. Previously, we identified the melanocyte lineage-specific antigen gp 100 that is expressed by both melanoma cells and normal melanocytes, as a target antigen for tumor-infiltrating lymphocytes derived from a melanoma patient (TIL 1200). Here, we demonstrate that the oligoclonal HLA-A2.1-restricted TIL 1200 line is reactive with 2 distinct peptides derived from the gp 100 protein. Apart from the peptide corresponding to gp 100 amino acids 457-466, we identified the gp 100 peptide 154-162 as a second epitope recognized by TIL 1200. A 100-fold lower concentration of this novel gp 100 peptide was required for target-cell sensitization compared to peptide 457-466, indicating that the 154-162 peptide is the dominant gp 100 epitope for TIL 1200. Together with the recently described gp 100 280-288 epitope, 3 distinct CTL epitopes have now been identified in gp 100, all presented in the context of HLA-A2.1. Therefore, gp 100 is an attractive target antigen in the development of immuno-therapeutic protocols against melanoma.
Bakker
A B
AB
Department of Tumor Immunology, University Hospital Nijmegen St. Radboud, The Netherlands.
Schreurs
M W
MW
Tafazzul
G
G
de Boer
A J
AJ
Kawakami
Y
Y
Adema
G J
GJ
Figdor
C G
CG
D000595:Amino Acid Sequence; D001483:Base Sequence; D000939:Epitopes; D015234:HLA-A Antigens / Q000032:analysis*; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D000939:Epitopes; D015234:HLA-A Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen