Cytotoxic T lymphocytes define multiple peptide isoforms derived from the melanoma-associated antigen MART-1/Melan-A

Int J Cancer. 1999 Jun 11;81(6):979-84. doi: 10.1002/(sici)1097-0215(19990611)81:6<979::aid-ijc22>;2-y.


Peptides derived from the melanoma-associated MART-1/Melan-A antigen are currently implemented in immunotherapy for inducing or augmenting T-cell responses directed against peptides expressed by autologous tumor cells in HLA-A2+ patients with melanoma. Here, we describe the specificity of the T-cell clone SK29-FFM1.1, which secretes GM-CSF in response to a panel of synthetic MART-1/Melan-A-derived peptides, including the naturally presented ILTVILGVL(32-40), but exhibits cytotoxicity and IFN-gamma secretion exclusively to the MART-1/Melan-A derived peptide AAGIGILTV(27-35). In addition, cytotoxic T-lymphocyte (CTL) clone SK29-FFM1.1 recognizes 3 different naturally processed and presented peptides on HLA-A2+ MART-1/Melan-A+ melanoma cells, as defined by cytotoxicity and IFN-gamma and GM-CSF secretion. Processing and presentation of MART-1/Melan-A peptides appears to be different in cells of non-melanocytic origin, as shown by the characterization of naturally presented peptides displayed by HLA-A2+ colorectal cancer cells transduced with a MART-1/Melan-A gene-containing retrovirus. Our data suggest that multiple epitopes, including ILTVILGVL and different isoforms of AAGIGILTV derived from MART-1/Melan-A may be naturally presented by melanoma cells to the immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm
  • Clone Cells
  • Cytotoxicity, Immunologic
  • HLA-A2 Antigen / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • MART-1 Antigen
  • Melanoma / genetics*
  • Melanoma / immunology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Recombinant Proteins / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • HLA-A2 Antigen
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Protein Isoforms
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Proteins
  • Interferon-gamma