Identification of a shared HLA-A*0201-restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 (TRP2).

Abstract

Tyrosinase-related protein 2 (TRP2) is a melanosomal enzyme expressed in most mammalian melanocytes and melanomas. This protein has been identified as a melanoma antigen recognized by tumor reactive CTLs derived from tumor infiltrating lymphocytes in the context of HLA-A31 and HLA-A33. The frequencies of these HLA-A alleles among melanoma patients in the United States is low (approximately 6% for HLA-A31 and approximately 2% for HLA-A33) compared with that of HLA-A*0201 (approximately 46%). Therefore, to extend significantly the use of TRP2-based immunotherapies for the treatment of patients with melanoma, we searched for new HLA-A*0201-restricted epitopes from this protein by screening TRP2-derived peptides for the induction of melanoma-reactive CTL. Fifty-one peptides were selected from TRP2 based on a permissive HLA-A*0201 binding motif, and the 21 peptides with the highest experimentally determined binding affinities were used to stimulate peripheral blood lymphocytes from HLA-A*0201+ melanoma patients in vitro. One peptide, TRP2(180-188) (SVYDFFVWL), induced CTLs from three of four patients that specifically recognized peptide-pulsed T2 cells, COS-7 cells expressing HLA-A*0201 and TRP2, and HLA-A2+ TRP2+ melanomas. TRP2(180-188) is identical to a previously identified TRP2 epitope recognized by murine melanoma-reactive CTLs in the context of H-2Kb. These results suggest that TRP2 may be useful for the development of murine tumor immunotherapy models and for the treatment of melanoma patients who are diverse in HLA expression.

• Authors: M R Parkhurst, E B Fitzgerald, S Southwood, A Sette, S A Rosenberg, Y Kawakami
• Journal: Cancer research (Cancer Res) Vol. 58 Issue 21 Pg. 4895-901 (Nov 01 1998) ISSN: 0008-5472 [Print] United States
• PMID: 9809996 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• HLA-A Antigens
• Peptide Fragments
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Antigens, Neoplasm (immunology)
• Epitopes, T-Lymphocyte
• HLA-A Antigens (immunology)
• Humans
• Intramolecular Oxidoreductases (immunology)
• Melanoma (immunology)
• Peptide Fragments (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured