Obiettivo Cytomegalovirus (CMV) is a ubiquitous herpesvirus, latently persisting in the majority of the adult population worldwide. In these hosts, CMV-specific memory cells dominate the immune memory compartment. It follows that CMV-specific T-cells dominate the memory compartment of the majority of the human population worldwide.I propose to define within this project the molecular mechanisms driving the inflation of CMV-specific T-cells. My central hypothesis is that expression levels of CMV peptides during latency, along with the avidity of T-cell receptors for peptide MHC complexes, define the amplitude of T-cell responses. A corollary hypothesis is that vigorous T-cell responses in CMV infection are defined by factors that drive CMV gene expression during latency, such as inflammatory stimuli.This hypothesis will be verified in a model of in vivo CMV latency and immune monitoring. We will benefit from state-of-the-art inducible genetic systems, where recombinant mouse CMV will be deployed in transgenic mice. In latently infected mice, we will induce or suppress the expression of immunodominant CMV genes, and define downstream effects on T-cell response kinetics. In parallel, we will define the T-cell responses to high and low avidity peptides.Understanding the mechanisms driving the strong T-cell response to CMV is of outstanding biological and clinical relevance. If strong T-cell responses may be redirected to target heterologous antigens of interest, CMV-based vaccine vectors might potentially allow the development of HIV or tumor vaccines. On the other hand, it is speculated that the control of latent CMV may overcommit the aging immune system and exhaust the T-cell repertoire. Given the CMV pervasiveness, discerning the mechanisms of its T-cell induction may define novel molecular targets for rejuvenation strategies. In either case, the proposed research has groundbreaking potential in the field of infection and immunity. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesmedical and health sciencesbasic medicineimmunologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines Programma(i) 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) Argomento(i) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Invito a presentare proposte ERC-2010-StG_20091118 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Contributo UE € 1 498 456,00 Indirizzo INHOFFENSTRASSE 7 38124 Braunschweig Germania Mostra sulla mappa Regione Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Tipo di attività Research Organisations Ricercatore principale Luka Cicin-Sain (Dr.) Contatto amministrativo Michael Straetz (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Germania Contributo UE € 1 498 456,00 Indirizzo INHOFFENSTRASSE 7 38124 Braunschweig Mostra sulla mappa Regione Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Tipo di attività Research Organisations Ricercatore principale Luka Cicin-Sain (Dr.) Contatto amministrativo Michael Straetz (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato