In the thymus, where central tolerance is generated, the medullar epithelial cells (mTEC) are involved in the deletion of self reactive T cells that recognize peripheral antigent, expressed by these cells during maturation. Natural regulatory cells are also generated in the thymus but their ligands are so fa unknown, as is the repertoire of autoantigenic peptides expressed in the thymus. Within this repertoire, peptides recognized with low affinity allow the formation of the circulating T cells, whereas Tregs recognize ligands with higher affinity. Whether the same peptides are recognized by both cell populations is not known. Our previous results in autoinmune thyroids indicate that in the target tissues of organ-specific autoimmnunity, recognize these complexes have not been identified. In this project we aim to study the influence of peptides presented by class II in autoimmune thyroids and their possible role in the generation, maintenance or breakdown of immunological tolerance. We'll try to identify to possible central or peripheral tolerance mechanisms against molecules of tissue restricted expression and therefore relevant for organ-specific autoimmunity. The study will be done on human material: thymus, lymphoid organ (spleen) and target organs (thyroid). The specific objectives are: (i) to phenotypically characterize T cells capable of recognizing peptides presented by DR in autoimmune thyroid; (ii) to analyze the DR-associated peptide repertoires in human thymus, trying to identify stromal specific peptides by comparing with those isolated from hematopoietic cells (...)
|Effective start/end date
|1/10/06 → 30/09/09
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