The Study Of Mimotope Peptides Of Keratin Which Specifically Bind To The Anti-keratin Antibodies Screened From Phage Random Peptide Library

T cell infiltrates are an important feature of psoriasis- a complex disease with diverse clinical presentations and with polygenic inheritance. Increasing evidences indicate that T cell activation plays a key role in the pathogenesis of psoriasis. The strongest evidence linking T cell activation in psoriasis has been derived from the clinical observation that immunosuppressive drugs such as anti-CD3 mAbs, anti-CD4 mAbs, corticosteroids and cyclosporine A that inhibit T cell activation and cytokine release are effective treatments for psoriasis. The most convincing demonstration of this point is the experiment result that an IL-2-fusion toxin which had eliminated activated IL-2 receptor-positive T cell induced significant clinical resolution of psoriasis, meanwhile eliminated the dermal and intradermal T cell populations and reversed the regenerative epidermal phenotype. On the other hand, it was found that the activated autologous CD/ T cell lines can induce characteristic psoriatic plaques in uninvolved psoriatic skin transplated on mice with severe combined immunodeficiency (SCID). Furthermore, the psoriatic lesions can be maintained by injection of T cells obtained from psoriatic skin butnot by T cells from the blood of psoriatic patients.Within the normal epidermis there are differences in keratin expression. Keratins 5 and 14 are characteristically produced in the basal layer, keratins 1 and 10 are synthesized suprabasally. Hyperproliferation of keratinocytes is a characteristic feature of psoriatic epidermis and is associated with an altered programme of keratinocyte differentiation. In psoriasis there is an increased expression of keratin 14 and a novel suprabasal expression of the hyperproliferative keratins 6 and 16 with a corresponding reduction of keratins 1 and 10. In contrast to normal skin, keratin 17 is expressed in suprabasal keratinocytes in psoriatic lesions. Therefore, it is postulated that the critical self-epitopes on the homologous amino acid sequence among Keratins 6,14,16 and K17 may play an important role in the activation of CD/ T cells of psoriatic skin. On the other hand, streptococcal infection is a well-known trigger of guttate psoriasis, and guttate psoriasis may precede chronic plaque psoriasis. These clinical observations could be explained at least in part by immunological cross-reactivity between streptococcal M protein and human epidermal keratin. Psoriasis can be triggered by Streptococcal infection, then these cross-reactivities might be relevant to the pathogenesis of post-streptococcal psoriasis. Recently it is reported that an synthetic peptides from keratin 17 that shares the homologous sequence with keratin 14 and streptococcal M protein may be a major target for CD4+ T cells in psoriasis.Natural autoantibodies (NAA) are defined as antibodies that are present in the serum of healthy individuals and can bind to one or more self-antigens in the absence of deliberate immunization. They are encoded by germline genes and show preferential recognition of evolutionarily conserved crossreactive epitopes. As a member of NAA, anti-keratin auto antibodies (AK auto Ab) may recognize more than one epitope in the high conserved amino acid sequence region of keratin. It ispostulated that these epitopes recognized by AK auto Ab contain the critical self-epitope that can activate the CD4+ T cells of psoriatic skin. In order to identify the assumption, we must acquire the mimotopes of keratin recognized by AK auto Ab first of all.The research of epitope biology using the technology of random phage peptide library has been widely applied. The latest research results reveal that the linear oligopeptide expressed by phage can not only induce the same strong specific immunity just as the assembled epitope of the natural antigen does, but also mimic the epitope including glycosyl or chemical-modificated peptides. It is so called mimotope. Oligopeptide containing mimotope with high antigenicity can substitute for large antigen segment to be used in the study of novel pe...