Melanocyte-associated T cell epitopes can function as autoantigens for transfer of alopecia areata to human scalp explants on Prkdc(scid) mice.
Alopecia areata is a tissue restricted autoimmune condition affecting the hair follicle, resulting in hair loss. The goal of this study was to test the hypothesis that the autoantigen of alopecia areata is melanocyte associated. Potential autoantigens were tested in the human scalp explant/Prkd(scid) CB-17 mouse transfer system. Scalp T cells from lesional (bald) alopecia areata scalp were cultured with antigen-presenting cells, and antigen, along with interleukin-2. The T cells were then injected into autologous lesional scalp grafts on SCID mice, and hair regrowth was measured. Hair follicle homogenate was used as an autoantigen control. T cells cultured with melanoma homogenate induced statistically significant reduction in hair growth (p <0.01 by ANOVA). HLA-A2-restricted melanocyte peptide epitopes were then tested with lesional scalp T cells from HLA-A2-positive alopecia areata patients. Melanocyte-peptide-activated T cells significantly reduced the number of hairs regrowing in two experiments with six patients (p <0.001 by ANOVA). Injected scalp grafts showed histologic and immunochemical changes of alopecia areata. The most consistent peptide autoantigens were the Gp100-derived G9-209 and G9-280 peptides, as well as MART-1 (27-35). Melanocyte peptide epitopes can function as autoantigens for alopecia areata. Multiple peptides were recognized, suggesting epitope spreading.
Gilhar
A
A
Skin Research Laboratories, Flieman Medical Center and Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
Landau
M
M
Assy
B
B
Shalaginov
R
R
Serafimovich
S
S
Kalish
R S
RS
D000328:Adult; D000506:Alopecia Areata / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000494:pharmacology; D002457:Cell Extracts; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma; D051379:Mice; D016513:Mice, SCID; D012535:Scalp / Q000166:cytology / Q000637:transplantation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured
D001324:Autoantigens; D002457:Cell Extracts; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen