A subset of T cells, expressing the transcription factor Foxp3, dampens immune responses in an antigen specific manner. These cells are first selected in the thymus through interaction with MHC-peptide expressed locally and therefore encompass a TCR repertoire enriched in self-reactivities. Yet, a wide array of molecules produced by commensals, brought in by food or expressed by the fetuses is also tolerated by the immune system. This paradox calls for a formal evaluation of the rules governing Treg differentiation, their maintenance and expansion as well as their domain of competences. Our specific aims are: 1) to establish the origin of the antigens that drive regulatory T cells differentiation; 2) to establish the origin of regulatory T cell specific to strictly peripheral antigens; 3) along with the hygiene theory, to test the role of the microbiota in modulating immune tolerance; 4) to asses the role of B cells and B cell products in the control of T cell homeostasis. Building from the finding produced by these investigations we aim at improving peptide therapies for autoimmune disease.
The use of specific monoclonal Antibodies, a class of “biologicals”, in the treatment of autoimmune patients has provided spectacular clinical results. However a large fraction of patients develop an immune response against the drug and produce antibodies reverting the benefit of the therapy. We aim at assessing the relevance of drug immunogenicity in clinical practice in Portugal.