Antagonists of NR2F6 For Augmenting The Immune Response

A method for identifying immuno-augmenting agents comprising

• (a) contacting a cell, tissue or a non-human animal comprising a reporter construct for NR2F6-inhibition with a candidate molecule;
• (b) measuring the reporter signal;
• and
• (c) selecting a candidate molecule which alters the reporter signal.

A method for assessing the activity of a candidate antagonist of NR2F6 comprising the steps of:

• (a) contacting a cell, tissue or a non-human animal comprising NR2F6 with said candidate;
• (b) detecting a decrease in NR2F6 activity or an increase in the activity and/or expression of at least one component of the NR2F6-dependent intracellular signalling cascade;
• and
• (c) selecting a candidate that decreases NR2F6 activity or increases the activity and/or expression of at least one component of the NR2F6-dependent intracellular signalling cascade;
• wherein a decrease of the NR2F6 activity or increase of the activity and/or expression of at least one component of the NR2F6-dependent intracellular signalling cascade is indicative for the capacity of the candidate to augment immune response.

A reporter construct for detection of NR2F6-inhibition comprising:

• (a) a ligand-mediated reporter gene expression construct comprising an NR2F6-promoter reporter and consecutively expressed NR2F6, whereby a change in ligand binding to said NR2F6-promoter reporter leads to a change in reporter signal;
• (b) a ligand displacement construct comprising a ligand-binding domain of NR2F6 and a nuclear receptor-ligand or co-receptor protein, whereby displacement of said nuclear receptor-ligand or co-receptor protein from said ligand-binding domain of NR2F6 leads to a fluorescence polarization (FP) or scintillation proximity (SP) signal;
• (c) a fluorescent cellular sensor fusion mutant construct comprising a reporter protein that is fused to a ligand-binding domain of NR2F6, whereby binding of a ligand to said ligand-binding domain of NR2F6 leads to a change in reporter signal;
• or
• (d) a ligand-induced homo- and/or heterodimer construct comprising a NR2F6 or a dimerization-capable part thereof and a dimerization partner of NR2F6, whereby dimerization of said NR2F6 or said part thereof and said dimerization partner of NR2F6 leads to a fluorescence resonance energy transfer (FRET) signal.