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Molecular mechanism...
Molecular mechanisms and complete antigen formation in allergic contact dermatitis
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- Ahlfors, Stefan (författare)
- Lund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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(creator_code:org_t)
- ISBN 9789186059583
- 2008
- Engelska 110 s.
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Serie: Lund University Faculty of Medicine Doctoral Dissertation Series, 1652-8220
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Abstract
Ämnesord
Stäng
- Allergic contact dermatitis (ACD) is a common T cell mediated skin disease. Small reactive organic molecules called haptens induce ACD. Haptens are not recognized by themselves, but need to bond to endogenous proteins in the skin, and processed further into complete antigens. Antigen specific T cells then recognize the resulting antigen. Although the haptens are well known, the chemical reactions of haptens inducing ACD is not well known. Neither are the chemical structures of the complete antigens associated with ACD in humans. This study is composed of three parts. Reactivity study of strong sensitizers like 2,4-dinitrofluorobenzene (DNFB), 1,4-benzoquinone (BQ), 4-t-butyl-1,2-benzoquinone (tBuBQ) and cis-1,2-hexahydrophthalic-anhydride (HHPA) under physiologic conditions with nucleophilic amino acids and peptides by analytical methods (HPLC, LC/MS/MS). The new reaction products were isolated and their structures were determined by NMR and MS. We found that most haptens reacted predominantly with cystein and cystein containing peptides. We then synthesized an array of 2,4-dinitrophenyl- (Dnp) modified collagen II peptides, as complete antigens, by solid phase peptide synthesis (SPPS). In a MHC class II (H2-Aq) restricted T cell model of ACD, we evaluated the responses of these antigens. The length of the amino acid side chain bonding the Dnp-group determined the T cell response. Substitution of lysine for ornithine gave a complete loss of T cell recognition. We finally used homology modeling to construct a model of the H2-Aq/antigen/TCR complex, a part of the ”immunological synapse”. Our new model could explain the experimental T cell responses in terms of a defined structure of the MHC/antigen, and how this structure is displayed for the TCR. This study may contribute to better diagnosis, and possibly a cure of ACD in the future.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
Nyckelord
- hypersensitivity
- adduct
- immune response.
- Allergy
- hapten
Publikations- och innehållstyp
- dok (ämneskategori)
- vet (ämneskategori)
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