HLA DR B1*04,*07-restricted epitopes on Keratin 17 for autoreactive T cells in psoriasis

Background: Psoriasis is a T cell-mediated inflammatory skin disease. Recent evidence suggests that activated CD4+ helper T lymphocytes of the Th1 phenotype play an important role in the pathogenesis of the disease. For psoriatic autoreactive T cells, Keratin 17 is a major target antigen and an epitope containing ALEEAN sequence has been described, but other psoriasis-related epitopes are stilt unknown. Objective: To identify the HLA DR B1*04, *07-restricted T cell epitopes on Keratin 17. Methods: HLA DRB1*04, *07-restricted T cell epitope regions on Keratin 17 were predicted based on related softwares and internet servers. Keratin 17 gene was amplified from psoriatic epidermis and the proteins of the predicted epitope regions were expressed, identified and purified. T cells from psoriatic patients reacted in cultivation with peptide-major histocompatibility complex (p-MHC) compound, then the level of cell proliferation and the concentration of interferon-gamma in culture supernatant were detected. After the psoriasis-related epitope regions were narrowed down, the epitopes on them were predicted further. These epitopes were then expressed and validated by T cell response in vitro. Results: Four epitopes-S1 (118-132), S2 (169-183), S4 (323-337) and S4 (348-362) can stimulate the proliferation and interferon-gamma production of psoriatic T cells more effectively than other epitopes (p < 0.01) and react weakly with the T cells from healthy volunteers (p > 0.05). Conclusion: Epitopes S1 (118-132), S2 (169-183), S4 (323-337) and S4 (348-362) are immunodominant DR B1-restriced T cell epitopes for psoriasis. Among them, S1 (118-132) contains the ALEEAN sequence while the others with different amino acid sequence have not been reported before. Further studies based on these peptides would provide a more complete understanding of the immunological basis of psoriasis. (c) 2005 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.