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

Maria R. Parkhurst, Ellen B. Fitzgerald, Scott Southwood, Alessandro Sette, Steven A. Rosenberg, Yutaka Kawakami

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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 (~6% for HLA-A31 and ~2% for HLA-A33) compared with that of HLA-A*0201 (~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(180188) (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(180188) 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.

Original languageEnglish
Pages (from-to)4895-4901
Number of pages7
JournalCancer Research
Volume58
Issue number21
Publication statusPublished - 1998 Nov 1

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Parkhurst, M. R., Fitzgerald, E. B., Southwood, S., Sette, A., Rosenberg, S. A., & Kawakami, Y. (1998). Identification of a shared HLA-A*0201-restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 (TRP2). Cancer Research, 58(21), 4895-4901.