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.