Immunology Discovery


T Cell Receptor Profiling for Immunology Discovery

Our expertise is a critical and complex component of the human adaptive immune system: the T lymphocyte. We have developed a proprietary technology platform that allows us to functionally identify and map cognate epitopes of human T cell receptors (TCRs) at unprecedented speed and accuracy. As a result, we can profile patient-derived TCR repertoires against large libraries of putative target epitopes.

Potential Applications

  • Fast, robust TCR discovery and characterization
  • Validation of predicted TCR:epitope interactions
  • Functional epitope mapping
  • Chimeric antigen receptor (CAR) evaluation
  • Safety profiling of TCR therapies
  • De novo TCR ligand identification, minimal epitope resolution
  • Customized TCR-based drug discovery programs

What is unique about our new technology platform?

Identification of the target epitope(s) of a given T cell receptor (TCR) is a major challenge. In contrast to antibodies, which bind directly to their target, T cells recognize processed peptide epitopes presented by class I and II HLA molecules. Most attempts described in the literature to make this interaction amenable to high-throughput screening are based on engineered variants of the T cell receptors and/or peptide:HLA complexes, or a priori knowledge of the epitope and/or presenting HLA allele, limiting their ability to fully catalog physiologically relevant TCR:target interactions.

In contrast, our new technology platform more closely represents the physiological processes underlying antigen processing, presentation, and ligand-induced T-cell activation.

Our patent-pending platform consists of three major components:

1. T Cell Reporter Construct

Our reporter cassette is designed such that any exogenous TCR or chimeric antigen receptor (CAR) can be inserted into the system. Based on a highly sensitive and specific synthetic promoter, engagement of the inserted receptor produces a fluorescent signal with an unprecedented signal-to-noise ratio easily detected by flow cytometry and/or microscopy. At the same time, the activated T cells produce a secreted label that binds to the cognate antigen-presenting cell(s).

2. Antigen-Presenting Cell Construct

As a starting point for this construct, we use immortalized antigen-presenting cells from the TCR-autologous donor or our biobank, which currently covers approximately 80% of the most frequent HLA alleles. Following transduction with our patent-pending minigene library construct, these cells process and present peptides from the encoded antigens efficiently and persistently on both class I and II HLA. As a unique feature, we have identified and overcome a size limitation constraint on cDNA-derived antigen processing. As a result, we reliably achieve epitope presentation from open reading frames up to 400 amino acids in length, enabling library design that can feasibly cover the entire human reference proteome.

3. Phenotypic Screening Platform

Next-generation sequencing of enriched target antigens is a powerful readout for high-throughput screening, but can be time-consuming and noisy. For targeted applications in which this is undesirable, we have developed a combinatorial phenotypic screening approach that unambiguously identifies the cognate target(s) with up to 98% first-pass confidence. This enables quick and cost-efficient profiling of TCRs against relatively large antigen libraries.

What are potential applications?

Our platform is particularly useful in biomedical research and drug discovery in oncology (tumor vaccines, targeted cancer immunotherapy, CAR-T, and TCR-T cell therapy), autoimmunity (autoantigen discovery, targeted immune modulation, regulatory TCR-T cell therapy), and infectious diseases (vaccines, chronic infection). Its modular design additionally provides the platform with the flexibility to easily incorporate alternative antigen-presenting cells, scales of throughput, and multiplexing options. Whenever the specificity of a T cell response in patients is of interest, our technology can provide valuable new insights.

How can we support your research and development?

Our preferred business model is to perform customized research projects on a fee-for-service basis. At the end of a project, our customers acquire full ownership of the results at pre-defined terms without the obligation of royalty or milestone payments.

Interested in discussing potential projects?

Please contact us and find out what we can do for you!

Dr. John M. Lindner

Head of Immunology Discovery

Our Team Members

Dr. John M. Lindner

Head of Immunology Discovery

 Short Bio
  • 2018 – 2022: Group Leader of team IAA (Rapid Identification of Auto-Antigens in Autoimmune Diseases) at the BioMed X Institute, Heidelberg, Germany
  • 2014 – 2018: Postdoc in autoimmune antibody repertoires with Dr. Elisabetta Traggiai at the Novartis Institutes for BioMedical Research, Basel, Switzerland
  • 2008 – 2013: PhD (molecular immunology) in B-cell transcriptional control with Dr. Peter Nielsen in the Department of Prof. Michael Reth at the Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

Dr. Taga Lerner

Postdoctoral Researcher

 Short Bio
  • 2016 – 2021: PhD in RNA editing in macrophages with Prof. Nina Papavasiliou, Department of Diversification in Immunity at the DKFZ, Heidelberg, Germany
  • 2015 – 2016: Scientific Technical Editor, Henry Stewart Talks, Herzliya, Israel
  • 2011 – 2014: Master of Science in Microbiology and Clinical Immunology at Tel Aviv University, Tel Aviv, Israel

Dr. Theresa Schmid

Postdoctoral Researcher

 Short Bio
  • 2017 – 2021: PhD (Bioscience) focusing on epigenetics in cancer with Prof. Peter Lichter at the DKFZ, Heidelberg, Germany
  • 2014 – 2017: Master of Science (Molecular Biology) at Johannes -Kepler University, Linz and Paris Lodron University, Salzburg
  • 2011 – 2014: Bachelor of Science (Molecular Bioscience), Johannes -Kepler University, Linz, Paris Lodron University, Salzburg and Max Planck Institute of Psychiatry, Munich

Georgios Samaras

Research Assistant

 Short Bio
  • 2020 – 2021: Master of Science in Translational Medical Research at Medical Faculty of Mannheim, University of Heidelberg, Germany
  • 2015 – 2020: Bachelor of Science in Molecular Biology and Genetics at Democritus University of Thrace, Greece

Clàudia Maldonado Torres

Research Assistant

 Short Bio
  • 2021 – 2022: Research Assistant in team RSC (RNA Splicing in Cancer) at the BioMed X Institute, Heidelberg, Germany
  • 2020 – 2021: Master’s degree in Translational Biomedical Research at Vall d’Hebron Research Institute (VHIR) in Barcelona, Spain.
  • 2016 – 2020: Bachelor’s degree in Biomedical Sciences at the University of Barcelona (UB), Spain
Image of