CD4+ T-cells from peripheral blood of a patient with psoriasis recognize keratin 14 peptide but not 'homologous' streptococcal M-protein epitope |
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Authors: | Kobayashi Hiroya Takahashi Michinari Takahashi Hidetoshi Ishida-Yamamoto Akemi Hashimoto Yoshio Sato Keisuke Tateno Masatoshi Iizuka Hajime |
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Affiliation: | a Department of Pathology, Asahikawa Medical College, 2-1-1 Midorigaoka-Higashi, Asahikawa, Japan b Department of Dermatology, Asahikawa Medical College, 2-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan |
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Abstract: | Psoriasis has been recognized as an immunologically mediated inflammatory skin disease that has been associated with group A, β-haemolytic streptococcal infections. Notably cross-reactive autoimmune mechanism, which is mediated by T cells reacting to epitopes that are common to streptococcal M-protein and keratin, has been proposed in psoriasis. In order to investigate this possibility, peptides corresponding to M-protein and human epidermal keratin, which share some amino acid sequence between them, were synthesized and tested for their ability to stimulate T-cells of patients with psoriasis. Among five cases examined, we isolated a CD4+ T-cell line that recognized the type I keratin (K14)p168–181 when it was presented by the patient's HLA-DR molecules from a single psoriatic patient, whose MHC allele was HLA-A2/A26, -B27/B16, -DR4/DR8, -DQ8. Further analysis disclosed that the critical peptide recognized by the T-cell line was 10-mer keratinp171–180 (DLRNKILTAT). However, corresponding M6 protein with homology to K14 did not stimulate the T-cell response and no evidence for cross-reactivity was obtained. The K14-responsive T cell line produced IFN-γ, but little IL-4 when stimulated with irradiated autologous PBMC pulsed with this peptide. Thus, the finding that human epidermal keratin peptide is immunogenic in a psoriasis patient may provide the evidence that T lymphocytes play an important role in the pathogenesis of psoriasis as an autoimmune disorder participated with Th1 like cells. However, the keratin-responsive T cell line was detected in only one of five cases of psoriasis examined, suggesting that such T cell line appears to be not so popular in psoriatic patients. No evidence for cross-reactivity to streptococcal M protein also suggests that the contribution of streptococci may simply be inducing proliferation of various repertoire of T cells (including K14-responsive T cells) possibly through a superantigen-dependent process. |
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Keywords: | T cell Peptide Keratin |
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