Objective
The current paradigm of T cell function in the immune response is that T cells recognize antigen through the T cell antigen receptor (TCR) which transduces signals to the cytoplasm by way of cytosolic priming and effector tyrosine kinases. The TCR acts in a monovalent fashion is crosslinked by its antigen/MHC (pMHC) ligand, causing TCR triggering. However, our more recent data indicate that the TCR is organized in pre-existing oligomers, and therefore it might not require crosslinking, and that the triggered TCR adopts, upon ligand binding, an active conformation that is responsible for recruiting cytoplasmic effector molecules. We have found novel direct effectors of the TCR, including the Ras GTPase TC21 and unveiled that these effectors play an essential role in a variety of TCR signaling functions including tonic signaling and TCR downregulation. Furthermore, we have found that TC21 is required for the acquisition of pMHC by T cells from the APCs and re-express it on their own plasma membrane, becoming themselves APCs for other T cells. In this proposal we wish to explore several of the avenues open by our most recent findings, including the importance of pMHC presentation by T cells. Another objective is to study an interesting property of the conformational change in the TCR: its return to the inactive conformation even when it is still bound to its pMHC ligand (countdown effect). We also propose to use approaches that alter the size of pre-existing TCR oligomers to seek for new ways of modulating T cell activation. The last two objectives refer to study the role of TC21 as a direct effector of the B cell antigen receptor (BCR). We propose to study the involvement of TC21 in the B cell germinal center response and how the deregulation of its expression can influence the transformation of GC B cells into lymphomas. Finally, we propose to generate small molecular weight inhibitors of TC21 as potential drugs for the treatment of lymphomas.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2013-ADG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
28006 MADRID
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.