Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo

Belinda Palermo, Silvia Garbelli, Stefania Mantovani, Elisabetta Scoccia, Gian Antonio Da Prada, Paola Bernabei, M. Antonietta Avanzini, Valeria Brazzelli, Giovanni Borroni, Claudia Giachino

Research output: Contribution to journalArticlepeer-review

Abstract

Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: Cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor down-regulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-γ production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocyte-specific cytotoxic responses differs between the two pathologies.

Original languageEnglish
Pages (from-to)3153-3162
Number of pages10
JournalEuropean Journal of Immunology
Volume35
Issue number11
DOIs
Publication statusPublished - Nov 2005

Keywords

  • Autoimmunity
  • Melan-A/MART-1
  • TCR affinity
  • TCR down-regulation
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo'. Together they form a unique fingerprint.

Cite this