title: CD4+ T-cells from peripheral blood of a patient with psoriasis recognize keratin 14 peptide but not 'homologous' streptococcal M-protein epitope.
abstract: Psoriasis has been recognized as an immunologically mediated inflammatory skin disease that has been associated with group A, beta-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 keratin(p171-180) (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-gamma, 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.
authors.affiliation: Department of Pathology, Asahikawa Medical College, 2-1-1 Midorigaoka-Higashi, Asahikawa, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Michinari
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tateno
authors.forename: Hajime
authors.initials: H
authors.lastname: Iizuka
mesh_terms: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes; D006801:Humans; D053547:Keratin-14; D007633:Keratins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011565:Psoriasis / Q000097:blood* / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D000939:Epitopes; C507540:KRT14 protein, human; D053547:Keratin-14; D010446:Peptide Fragments; C014689:streptococcal M protein; D007633:Keratins