Identification of a novel gp100/pMel17 peptide presented by HLA-A*6801 and recognized on human melanoma by cytolytic T cell clones

M. Sensi, S. Pellegatta, C. Vegetti, G. Nicolini, G. Parmiani, A. Anichini

Research output: Contribution to journalArticle

Abstract

Melanoma-associated peptides recognized by cytolytic T lymphocytes (CTL) in the context of several histocompatibility leukocyte antigens (HLA) are required for the development of specific immunotherapies. Using a transient transfection assay into COS-7 cells, we identified the gp100/pMel17 melanosomal protein as the shared antigen recognized by three independent CD8+ CTL clones in HLA-A*6801-restricted fashion. This finding was confirmed by the correlation between lack of gp100/pMel17 protein in a number of HLA-A*6801-positive melanomas and their resistance to lysis/cytokine production by the specific effectors. The gp100/pMel17 antigenic epitope was identified based on recognition of subfragments and on a computer-based prediction algorithm. Among a panel of gp100/pMel17-derived synthetic peptides only the 10-mer HTMEVTVYHR (gp100/pMel17182-191) induced tumor necrosis factor (TNF) release by CTL clones when pulsed on suitable target cells whereas both the 10-mer and the shorter 9-mer gp100/pMel17183-191 sensitized the same antigen-pulsed cells to lysis. In conclusion, the identification of the HTMEVTVYHR peptide will extend to HLA-A*6801 melanoma patients the possibility to exploit gpl00/pMel17 melanosomal protein for experimental and clinical studies.

Original languageEnglish
Pages (from-to)273-279
Number of pages7
JournalTissue Antigens
Volume59
Issue number4
DOIs
Publication statusPublished - 2002

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Keywords

  • CTL
  • gp100/ Pmel17
  • HLA-A28
  • Melanoma
  • Tumor antigen

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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