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Interactions between hla-class ii and peptides: definition of functionally important epitopes implicated in susceptibility to chronic autoimmune diseases

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Short description of the additional proposal The main objectives of this proposal are the discovery and structural characterization of the MHC class II epitopes and superantigens that seem to be implicated in the development of Juvenile Rheumatoid Arthritis (JRA) and others autoimmune pathologues initiated by streptococcal M proteins.
For this reason a principally new method and software for comparative protein structure ana molecular mimicry studies will be elaborated based on the amino acid codon root code ( the second half of the genetic code ). The new methods will be used for studies of structural and functional organization of M proteins ( Ml,M5,M6,M24,M49 etc.), other bacterial and viral superantigens and MHC class II proteins (HLADR, -DQ, -DP etc.) and also tissue specific proteins.
Attempts will be made to identify (i) the locations of M proteins superantigenic sites involved in JRA pathology, (ii) the locations of M protein epitopes shared with protein of human miocardium and (iii) to test the hypothesis that functionally important epitopes have structutal elements characteristic for HLA - chain active site (region including amino acid 65-95). On the basis of obtained analitical data the design and synthesis of model peptides corresponding to revealed superantigenic and antigenic sites are envisaged.
Attempts using model peptides to induce symptoms characteristic for the superantigen action and JRA autoimmune pathology will be made (in cooperation with other participants of the present project abroad).

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UNIVERSIDAD COMPLUTENSE DE MADRID
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