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 affinities 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 amino acids (e.g. linear antigen sequence). Thereby no prior information about the nature of the antigen 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.