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.
Keywords
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Article info
Publication history
Accepted:
August 28,
2002
Received in revised form:
August 26,
2002
Received:
May 13,
2002
Identification
Copyright
© 2002 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
