METHOD FOR IDENTIFICATION OF TARGET ANTIGENS OF T-CELLS
T Cell mediated immunity plays a major role in infectious diseases, autoimmunity and tumor development. T cells can have a protective role but can also induce pathogenic effects. Therefore there is an urgent need for an unbiased strategy to determine the antigens of tissue-invasive lymphocytes. However, in contrast to the identification of antibody-ligands there is no generally applicable method for the characterization of the target antigens of T cells.
Two main peculiarities of T-cell receptors constitute an obstacle for this characterization: Firstly affi- nities of the T-cell receptors to their antigens are very low (several orders of magnitude lower than the affinities of antibody-ligand pairs) and secondly T-cell receptors recognize antigen sequences in a rather unspecific manner, meaning that not only one defined target sequence is recognized but several similar antigen sequences.
The inventors could establish a novel method for the identification of T-cell epitopes of 7-10 ami- no acids (e.g. linear antigen sequence). Thereby no prior information about the nature of the anti- gen entity required and an HTS method with extremely high sensitivity (one positive cell detected in 10,000,000 negative cells within a few hours) is offered.
- New diagnostic tools (biomarkers)
- Personalized therapies (e.g. patient-specific epitopes)
- High prognostic contribution on etiopathogenesis
- Applicable for following areas: tumor vaccination, infectious diseases, autoimmune diseases, phage and ribosome display methods
Proof of Concept in vivo
(1) Siewert, K. et al. Nat. Med. 18(5), 824-829 (2012); doi: 10.1038/nm.2720
(2) Rühl, G. et al. Neurol Neuroimmunol Neuroinflamm 3, 1-10 (2016); doi: 10.1212/NXI.0000000000000241