1. Division of Dermatology, Sunnybrook and Women's College Health Sciences Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
2. ^*Division of Molecular and Cellular Biology, Research Institute, Sunnybrook and Women's College Health Sciences Center, Department of Medicine, University of Toronto, Ontario, Canada
3. ^†Immunology Platform, Aventis Pasteur, Toronto, Ontario, Canada

Correspondence: Mark A. DeBenedette, PhD, Immunology Platform, Research Center, Aventis Pasteur Canada Ltd, Connaught Campus, 1755 Steeles Avenue West, Toronto, Ontario, Canada, M2R 3T4. Email: Mark.Debenedette@Aventis.com

Received 10 October 2002; Revised 28 February 2003; Accepted 16 April 2003; Published online 18 August 2003.

Abstract

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.