Cel 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. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesmedical and health sciencesbasic medicineimmunologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines Program(-y) 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) Temat(-y) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Zaproszenie do składania wniosków ERC-2010-StG_20091118 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Wkład UE € 1 498 456,00 Adres INHOFFENSTRASSE 7 38124 Braunschweig Niemcy Zobacz na mapie Region Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Rodzaj działalności Research Organisations Kierownik naukowy Luka Cicin-Sain (Dr.) Kontakt administracyjny Michael Straetz (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Niemcy Wkład UE € 1 498 456,00 Adres INHOFFENSTRASSE 7 38124 Braunschweig Zobacz na mapie Region Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Rodzaj działalności Research Organisations Kierownik naukowy Luka Cicin-Sain (Dr.) Kontakt administracyjny Michael Straetz (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych