Summary
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 still 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-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.
Results:
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).
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.
Keywords
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Article info
Publication history
Accepted:
January 6,
2005
Received in revised form:
December 27,
2004
Received:
October 28,
2004
Identification
Copyright
© 2005 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
