Cytotoxic T lymphocyte reactivity to gp100, MelanA/MART-1, and tyrosinase, in HLA-A2-positive vitiligo patients.
Vitiligo is a common depigmentation disorder thought to result from autoimmune destruction of melanocytes. Recent studies suggest a role for cell-mediated immune responses to melanocyte differentiation antigens, including gp100, MelanA/MART-1, and tyrosinase, in vitiligo pathogenesis. This study investigated T cell reactivity to MelanA/MART-1, tyrosinase, and gp100, in HLA-A2-positive patients with vitiligo. Melanocyte-specific T cell responses were measured ex vivo via enzyme-linked immunospot assay following stimulation with MelanA/MART-1, tyrosinase, and modified gp100 epitopes. Antigen-specific T lymphocyte reactivity to gp100 peptides was seen in 15 of 17 (88%) patients, with many demonstrating very high reactivity at levels comparable with those observed with common recall antigens. Reactivity to gp100 was noted to be associated with disease activity. Antigen-specific T lymphocyte reactivity to MelanA/MART-1 and tyrosinase peptides was not observed ex vivo in our patients, and only one patient demonstrated responses to MelanA/MART-1 and tyrosinase peptides following in vitro re-stimulation. Our findings implicate T cell reactivity to gp100 in patients with active disease and support the concept of an immunopathologic mechanism in vitiligo, in which cell-mediated responses to normal melanocyte antigens play a crucial part.
Mandelcorn-Monson
Rochelle L
RL
Division of Dermatology, Sunnybrook and Women's College Health Sciences Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Shear
Neil H
NH
Yau
Eddy
E
Sambhara
Suryaprakash
S
Barber
Brian H
BH
Spaner
David
D
DeBenedette
Mark A
MA
D000951:Antigens, Neoplasm; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D015789:HLA-A2 Antigen / Q000032:analysis*; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008544:Melanocytes / Q000737:chemistry / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology*; D014442:Monophenol Monooxygenase / Q000032:analysis / Q000276:immunology; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology*; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D001324:Autoantigens; D000939:Epitopes; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase