NOVARIPP

Novel properties of antigen receptors and instruments to modulate lymphoid function in physiological and pathological conditions

 Coordinatore AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS 

Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.

 Nazionalità Coordinatore Spain [ES]
 Totale costo 2˙491˙827 €
 EC contributo 2˙491˙827 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-ADG
 Funding Scheme ERC-AG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-02-01   -   2019-01-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

 Organization address address: CALLE SERRANO 117
city: MADRID
postcode: 28006

contact info
Titolo: Dr.
Nome: Balbino
Cognome: Alarcon Sanchez
Email: send email
Telefono: +34 911964555

ES (MADRID) hostInstitution 2˙491˙827.00
2    AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

 Organization address address: CALLE SERRANO 117
city: MADRID
postcode: 28006

contact info
Titolo: Ms.
Nome: Ana Maria
Cognome: De La Fuente
Email: send email
Telefono: +34 915681709

ES (MADRID) hostInstitution 2˙491˙827.00

Mappa


 Word cloud

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recent    signaling    antigen    cells    direct    effectors    tc    cell    tcr    oligomers    found    conformation    effector    pre    ligand    lymphomas    pmhc    receptor    apcs   

 Obiettivo del progetto (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.'

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