Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo
✍ Scribed by Belinda Palermo; Silvia Garbelli; Stefania Mantovani; Elisabetta Scoccia; Gian Antonio Da Prada; Paola Bernabei; M. Antonietta Avanzini; Valeria Brazzelli; Giovanni Borroni; Claudia Giachino
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 253 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
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 downregulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-c 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 melanocytespecific cytotoxic responses differs between the two pathologies.