Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo.
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-gamma 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.
Palermo
Belinda
B
Experimental Immunology Laboratory, IRCCS Maugeri Foundation, Pavia, Italy.
Garbelli
Silvia
S
Mantovani
Stefania
S
Scoccia
Elisabetta
E
Da Prada
Gian Antonio
GA
Bernabei
Paola
P
Avanzini
M Antonietta
MA
Brazzelli
Valeria
V
Borroni
Giovanni
G
Giachino
Claudia
C
D000951:Antigens, Neoplasm; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology*
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell