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 still unknown.
To identify the HLA DR B1*04, *07-restricted T cell epitopes on Keratin 17.
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-γ 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.
Four epitopes—S1 (118–132), S2 (169–183), S4 (323–337) and S4 (348–362) can stimulate the proliferation and interferon-γ 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).
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.
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- Response of murine and normal human skin to injection of allogeneic blood-derived psoriatic immunocytes: detection of T cells expressing receptors typically present on natural killer cells, including CD94, CD158, and CD161.Arch Dermatol. 1999; 135: 546-552
- HLA-DRB1 association in Turkish psoriasis vulgaris patients.Swiss Med Wkly. 2003; 133: 541-543
- The pathogenesis of psoriasis—investigating the genetics of a multifactorial disease.Duodecim. 2003; 119: 1517-1522
- Altered keratinocyte growth and differentiation in psoriasis.Clin Dermatol. 1995; 13: 105-114
- Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro.Br J Dermatol. 1995; 133: 501-511
- Current concepts in psoriasis and its treatment.Pharmacol Ther. 2003; 99: 133-147
- Skin T cell proliferative response to M protein and other cell wall and membrane proteins of group A streptococci in chronic plaque psoriasis.Clin Exp Immunol. 2001; 124: 516-521
- Psoriasis: a T-cell mediated autoimmune disease induced by streptococcal superantigens?.Immunol Today. 1995; 16: 145-149
- Psoriasis induced at the injection site of recombinant interferon gamma. Results of immunohistologic investigations.Arch Dermatol. 1990; 126: 351-355
- Circulating T cells of patients with active psoriasis respond to streptococcal M-peptides sharing sequences with human epidermal keratins.Scand J Immunol. 1997; 45: 688-697
- Is an epitope on keratin 17 a major target for autoreactive T lymphocytes in psoriasis?.Clin Exp Immunol. 1999; 117: 580-586
- Molecular cloning: a laboratory manual.2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY1989
- Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.J Clin Invest. 1998; 102: 1393-1402
- Dermal injection of immunocytes induces psoriasis.J Clin Invest. 1996; 98: 1878-1887
- The use of cyclosporin in psoriasis: a clinical review.Br J Dermatol. 2004; 150: 1-10
- HuMax-CD4: a fully human monoclonal anti-CD4 antibody for the treatment of psoriasis vulgaris.Arch Dermatol. 2003; 139: 1433-1439
- Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggest a primary immune, but not keratinocyte pathogenic basis.Nat Med. 1995; 1: 442-447
- Immunopathogenic mechanisms in psoriasis.Clin Exp Immunol. 2004; 135: 1-8
- Group A streptococcal antigen-specific T lymphocytes in guttate psoriatic lesions.Br J Dermatol. 1993; 128: 493-499
- Novel therapies for psoriasis.Am J Clin Dermatol. 2002; 3: 159-173
- Psoriasis induced at the injection site of recombinant interferon gamma.Arch Dermatol. 1990; 126: 351-355
- The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response.J Invest Dermatol. 1993; 101: 701-705
- Interferon-γ regulates expression of a novel keratin class I gene.Eur J Immunol. 1992; 22: 975-979
- Up-regulation of keratin 17 expression in human HaCaT keratinocytes by interferon-gamma.J Invest Dermatol. 1995; 104: 58-61
- Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide.Nature. 1994; 368: 215-221
- Promiscuous and allele-specific anchors in HLA-DR-binding peptides.Cell. 1993; 74: 197-203
- SYFPEITHI: database for MHC ligands and peptide motifs.Immunogenetics. 1999; 50: 213-219
- ProPred: prediction of HLA-DR binding sites.Bioinformatics. 2001; 17: 1236-1237
- Activation-induced cell death in T cells.Immunol Rev. 2003; 193: 70-81
- Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells.J Immunol. 1993; 150: 4338-4345
Accepted: January 6, 2005
Received in revised form: December 27, 2004
Received: October 28, 2004
© 2005 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.