Peptide diversityProject reference: 328866
Funded under :
Diversity of MHC/peptide complexes in thymic compartments and their role in shaping T cell repertoire
Total cost:EUR 161 968,8
EU contribution:EUR 161 968,8
Topic(s):FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development"
Call for proposal:FP7-PEOPLE-2012-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
Impaired selection of a functional and self-tolerant T cell repertoire is an underlying cause for development of immune system related disorders: immune-deficiencies and autoimmunity. However, current knowledge fails to explain how seemingly the same self-MHC/peptide complexes mediate the processes with completely different outcomes: survival versus apoptosis of T cells. In line, the nature of MHC/peptide complexes that mediate development of immune system and the influence of different antigen processing pathways on these complexes remain unresolved issues. The limitations of available technologies have left this question open. Recent advancement in the field of proteomics allows us now to precisely identify naturally occurring peptides that mediate selection of T cells. In addition, gene replacement technologies will be used to address the role of cathepsins, antigen-processing enzymes, on development of a fully functional T cell repertoire on one hand, and their effect on the quality and/or quantity of peptide epitopes displayed by cells that mediate T cell selection, on the other. The integration of proteomic methodology with in vivo experimental approach will enable us for the first time to interconnect the knowledge gained on cellular processes with direct physiological consequences in live animals. These new insights can accelerate not only discoveries related to T cell development, but are also relevant for understanding the interplay between T cells and pathogens, and can pave the way for new design and development of vaccines against infection diseases and therapies to treat autoimmunity. Thus, it directly contributes to strengthening European excellence in biomedical research. The host laboratory is one of the leading laboratories in the field of T cell biology that provides necessary expertise for successful realization of proposed project and the fellow has an outstanding track record of addressing questions related to immune-system related disorders.
EU contribution: EUR 161 968,8
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