Amino acid substitutions in the melanoma antigen recognized by T cell 1 peptide modulate cytokine responses in melanoma-specific T cells

Mai Britt Nielsen, Alexei F. Kirkin, Douglas Loftus, Mogens Holst Nissen, Licia Rivoltini, Jesper Zeuthen, Carsten Geisler, Niels Odum

Research output: Contribution to journalArticlepeer-review

Abstract

Single amino acid substitutions in melanoma-associated peptides dramatically enhance T-cell cytotoxicity against target cells presenting the modified peptides (often referred to as heteroclitic peptides). The authors tried to determine whether peptide modifications influence other aspects of T-cell immunity toward malignant melanoma. A heteroclitic peptide, E26F, with an E to F substitution in melanoma antigen recognized by T cell 1 (MART- I)26-35, triggers an enhanced tyrosine phosphorylation response when compared with the native- and other-modified MART-1 peptides. Similarly, the E26F peptide enhances the production of mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-γ and significantly enhances release of IL-13 and IL-10 from anti-MART-1 cytotoxic T cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-127-35, also enhances the tyrosine phosphorylation response in anti-MART-1 cytotoxic CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2-like cytokines (IL-10 and IL-13). Together these data show that minor amino acid modifications of immunodominant melanoma peptides profoundly influence the cytokine response in melanoma-specific T cells.

Original languageEnglish
Pages (from-to)405-411
Number of pages7
JournalJournal of Immunotherapy
Volume23
Issue number4
DOIs
Publication statusPublished - Jul 2000

Keywords

  • Cytotoxic T lymphocytes
  • Heteroclitic peptides
  • Immunotherapy
  • Interleukin- 10
  • MART-1

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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