Epithelial cells in organ-specific autoinmune diseases express ectopic MHC class II molecules, are targets of the tissue damage and are considered responsible of the maintenance of the response against autologus antigens. However, neither these autoantigens nor the function of the MHC molecules expressed by the epithelial cells are well defined in human autoinmune diseases. MHC class I and class II molecules are expressed on the cell surface associated with a short peptide whichm in infection, has been generated by degradation of antigens from the specific pathogen and, in physiological conditions comes from self molecules outside or inside the cell. The peptides associated to class II molecules expressed by ephitelial cells are as yet, unknown. Recently, several techniques have been developed which allow the identification of peptides naturally associated to class II molecules in cells constitutively expressing class II, consisting of an acid elution of low molecular weight material from class II molecules purified by immunoprecipitation. Sequencing the eluted peptides by mass spectromery has allowed the identification of the source proteins with very high resolution. In this project we propose the identification and characterization of peptides naturally associated to class II in epithelial cells from human autoimmune tissue as well as an epithelial cell line expressing human MHC-II by transfection. This is in order to identify autoantigens and T cell epiptopes in thyroid autoimmunity and IDDM. Knowledge of these epiptopes will be a giant step toward the developement of specific therapies as well as the study of the mechanisms underlying autoimmune processes.
|Effective start/end date||1/03/97 → 1/03/00|