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

Elke Jäger, Hanni Höhn, Julia Karbach, Frank Momburg, Chiara Castelli, Alexander Knuth, Barbara Seliger, Markus J. Maeurer

Research output: Contribution to journalArticlepeer-review

Abstract

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 ILTVILGVL32-40, but exhibits cytotoxicity and IFN-γ secretion exclusively to the MART-1/Melan-A derived peptide AAGIGILTV27-35. 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-γ 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.

Original languageEnglish
Pages (from-to)979-984
Number of pages6
JournalInternational Journal of Cancer
Volume81
Issue number6
DOIs
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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