Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes.
The infusion of TIL586 along with interleukin-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31-restricted CTL clone derived from the TIL586 cell line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide. Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.
Wang
R F
RF
National Cancer Institute, Bethesda, Maryland 20892, USA.
Appella
E
E
Kawakami
Y
Y
Kang
X
X
Rosenberg
S A
SA
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D015791:HLA-A3 Antigen / Q000276:immunology; D006801:Humans; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D000939:Epitopes; D015791:HLA-A3 Antigen; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011506:Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase