On AIRR 21: Cracking the TCR-epitope code with Hannah Meyer, Kilian Schober, and Hashem Koohy

Recorded live at the 4th Antwerp TCR meeting, this special panel episode brings together three leading experts in T-cell receptor (TCR) biology and computational immunology to explore one of the field's most challenging questions: Can we predict which epitopes a given TCR recognizes, and what would that unlock for medicine? Joining the discussion are: Dr. Hannah Meyer (Cold Spring Harbor Laboratory), whose research focuses on thymic selection and the mechanisms that shape a safe and functional T-cell repertoire. Prof. Kilian Schober (Friedrich-Alexander-Universität Erlangen-Nürnberg), a physician-scientist studying antigen-specific T-cell responses in infection, autoimmunity, and cancer. Prof. Hashem Koohy (University of Oxford), who applies computational and machine learning approaches to uncover the principles governing T-cell antigen recognition. Together, they discuss why TCR–epitope prediction remains one of immunology's grand challenges, despite rapid advances in AI and structural biology. Key topics covered include:  Why predicting TCR specificity is uniquely difficult, particularly because of HLA/MHC diversity Diagnostic value of epitope-TCR prediction across infectious disease, autoimmunity, and cancer How cross-reactivity links infectious disease, autoimmunity, and cancer immunology Why the biggest obstacle may be a lack of data rather than a lack of algorithms The difference between predicting and truly decoding TCR–epitope recognition New experimental and computational approaches What a future blood-test-based diagnostic platform might look like, and what it will take to get there Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. The episode is hosted by Dr. Ulrik Stervbo and Dr. Sofie Gielis.    Announcements and links Hannah Meyer https://meyer-lab-cshl.github.io/  Kilian Schober https://sites.google.com/view/schoberlab  Hashem Koohy https://www.rdm.ox.ac.uk/research/koohy-group-machine-learning-and-integrative-approaches-in-immunology Other: Antwerp TCR meeting https://www.uantwerpen.be/en/projects/audacis/antwerp-tcr-meeting/  Adaptive Immune Receptor Repertoire Community (AIRR-C) https://www.airr-community.org The Antibody Society (TAbS) https://www.antibodysociety.org AIRR-C Seminar Series https://www.antibodysociety.org/the-airr-community/airr-community-seminar-series/

In Episode 20 of On AIRR, Dr. Lauren Williamson and Dr. Robert Carnahan, both from Vanderbilt University Medical Center, and Dr. Matthew Vogt, from the University of North Carolina, share extreme stories of sample collection that reveal how cutting-edge therapeutic antibody development depends as much on donor generosity and complex global logistics as on scientific innovation. From dramatic efforts to secure the first U.S. donor samples in the early days of the COVID-19 pandemic, to rescuing lost samples from airport corridors and navigating international politics, these stories highlight the critical timing windows, global coordination, and human collaboration required to develop life-saving therapeutics. Throughout these extraordinary stories runs a thread of human generosity, demonstrating how crisis can bring out the best of human nature. Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.  Announcements and links Lauren Williamson https://www.vumc.org/crowe-lab/person/lauren-williamson-phd  Robert Carnahan https://www.vumc.org/crowe-lab/person/robert-carnahan-phd  Matthew Vogt https://www.vogtviruslab.com  Other: ReVAMPP  https://revampp.org Adaptive Immune Receptor Repertoire Community (AIRR-C) https://www.airr-community.org The Antibody Society (TAbS) https://www.antibodysociety.org AIRR-C Seminar Series: https://www.antibodysociety.org/the-airr-community/airr-community-seminar-series/

Episode 19 of onAIRR features a lively and insightful conversation with three outstanding scientists committed to advancing pandemic preparedness. Dr. Lauren Williamson and Dr. Robert Carnahan, both from Vanderbilt University Medical Center, and Dr. Matthew Vogt, from the University of North Carolina, share their passion for viral immunology and the art of discovering and developing therapeutic antibodies. onAIRR’s guests provide a behind-the-scenes look at how collaborative research is shaping the future of global health. They introduce the Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) research network, a major NIH-funded initiative aimed at strengthening pandemic readiness. The conversation explores the use of prototype pathogen approaches to identifying broadly neutralizing antibodies against high-priority viral families, the challenges of balancing breadth versus potency in therapeutic antibodies, and innovative screening methodologies that could transform our ability to respond to future pandemics. Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Announcements and links Lauren Williamson https://www.vumc.org/crowe-lab/person/lauren-williamson-phd Robert Carnahan https://www.vumc.org/crowe-lab/person/robert-carnahan-phd Matthew Vogt https://www.vogtviruslab.com ReVAMPP  https://revampp.org ReVAMPP https://www.niaid.nih.gov/news-events/nih-awards-establish-pandemic-preparedness-research-network  "Prototype Pathogen Approach for Vaccine and Monoclonal Antibody Development: A Critical Component of the NIAID Plan for Pandemic Preparedness” https://doi.org/10.1093/infdis/jiac296  Adaptive Immune Receptor Repertoire Community (AIRR-C) https://www.airr-community.org The Antibody Society (TAbS) https://www.antibodysociety.org AIRR-C Seminar Series https://www.antibodysociety.org/the-airr-community/airr-community-seminar-series

In this episode of On AIRR, Dr. Paul Thomas, reviews advances in the field of TCR sequencing. Dr. Thomas is a faculty member in the Department of Immunology of St. Jude Children’s Research Hospital. His work has advanced our understanding of innate and adaptive immune responses and TCR specificity with a focus on responses to viral infections. In Episode 18 of On AIRR, Dr. Thomas shares his journey from immunoparasitology to pioneering TCR repertoire sequencing. He began his scientific career studying innate immune responses to parasites during his graduate work in immunoparasitology. Motivated by a desire to use advanced molecular techniques, he moved to St. Jude for his postdoctoral research, where he contributed to the development of TCR repertoire sequencing methods. The discussion covers the evolution from single-chain TCR sequencing to the development of high-throughput paired sequencing methods, culminating in the TIRTL-seq approach. Dr. Thomas explains the technical and computational challenges in TCR pairing, the innovations that made large-scale studies possible, and the importance of data quality and curation in the field. The episode highlights the impact of these advances on understanding immune responses and the future of AIRR-based diagnostics. Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.  Announcements and links Paul Thomas Lab https://www.stjude.org/research/labs/thomas-lab.html  Other: TIRTL-seq: Deep, quantitative, and affordable paired TCR repertoire sequencing https://doi.org/10.1101/2024.09.16.613345   TIRTL-seq repository: https://github.com/pogorely/TIRTL Adaptive Immune Receptor Repertoire Community (AIRR-C) https://www.airr-community.org The Antibody Society (TAbS) https://www.antibodysociety.org AIRR-C Seminar Series s https://www.antibodysociety.org/the-airr-community/airr-community-seminar-series/

In this episode of On AIRR, Dr. Bjoern Peters, Professor at the La Jolla Institute for Immunology (LJI), explores how high-quality data serves as the foundation for advancing AI-based immunological predictions and diagnostics. Originally from Germany, Dr. Peters began his academic journey in theoretical physics at Hamburg, focusing on quantum optics, before pivoting to biophysics during his PhD at Humboldt University. This shift was inspired by the challenge of understanding epitope presentation pathways and the limitations of epitope-prediction algorithms, which led him to work with Dr. Alessandro Sette at LJI to develop the Immune Epitope Database (IEDB) — the world’s largest resource for immune epitope data. Throughout the conversation, Dr. Peters traces the evolution of epitope research, starting with his work on MHC-peptide binding predictions and expanding into broader immunological data collection. He emphasizes that high-quality datasets often outcompete algorithmic improvements and shares the story of how the IEDB was established to consolidate immune epitope data. The conversation explores the status of data standardization and use of ontologies in structuring biomedical data, particularly in immunology. Dr. Peters highlights how work done by the IEDB and the Adaptive Immune Receptor Repertoire Community (AIRR-C) in these areas is critical for advancing immunology and enabling prediction and diagnostics. Finally, the discussion covers challenges of predicting epitopes from immune repertoires, the growing interest in using AIRR sequencing for diagnostics, and the importance of rigorous, unbiased validation of prediction models for clinical applications.  Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.  Announcements and links Peters Lab https://www.lji.org/labs/peters-lab Tools mentioned: Immune Epitope Database (IEDB) https://www.iedb.org  Ontology for Biomedical Investigations (OBI) https://obi-ontology.org  Other: Adaptive Immune Receptor Repertoire Community (AIRR-C) https://www.airr-community.org The Antibody Society (TAbS) https://www.antibodysociety.org Antibody News Podcast, by TAbS https://www.antibodysociety.org/antibody-news-podcast Sette Lab https://www.lji.org/labs/sette-lab   

Dr. Thierry Mora and Dr. Aleksandra Walczak co-lead the Statistical biophysics group within Laboratoire de physique de l'ENS (LPENS) at the Ecole normale supérieure (Paris, France). Physicists by training, Dr. Mora and Dr. Walczak entered the field of the analysis of the immune system in a time when the first AIRR-seq datasets were becoming available. They have applied biophysics, neuroscience, and information theory perspectives to understand V(D)J recombination and quantify diversity. The group has published many software tools for the analysis of immune repertoires, including IGoR (to infer V(D)J recombination related processes from sequencing data), Sonia (infer selection pressures on features of amino acid CDR3 sequences), ALICE (detect TCR involved in immune responses from single RepSeq datasets), and PUBLIC (for analyzing sharing of TCRs, and predict public clones). In this episode of On AIRR, Dr. Mora and Dr. Walczak discuss the relevance and challenges of quantifying diversity and the questions that remain unanswered. They think of immune repertoire diversity in the same way as one could think of English language sentences, and try to learn the grammar of the combinations and quantify it. They also provide an overview of some of the software tools developed by their group. Comments are welcome to the inbox of [email protected]  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.   The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Announcements and links Statistical biophysics @ ENS. The website of the group. https://sites.google.com/view/statbiophysens/home Tools mentioned: IGoR: https://github.com/statbiophys/IGoR Sonia: https://github.com/statbiophys/SONIA SoNNia: https://github.com/statbiophys/sonnia ALICE: https://github.com/pogorely/ALICE PUBLIC: https://github.com/yuvalel/PUBLIC

Dr. Corey Watson is an Associate Professor at the University of Louisville. His work focuses on characterising and cataloguing antibody genetic diversity in human and mouse to better understand disease susceptibility and clinical health outcomes. Dr. William Lees is a researcher at University of London. His work focuses on developing Adaptive Immune Receptor (AIR) reference sets for diverse species and the annotation of experimental sequence data. In this episode we talk about the recent work by the Germline Database Working Group of the AIRR-Community. The accuracy of V and J gene segment assignment improves with the quality of the reference germline set. The accurate assignment is critical for characterization of somatic hypermutation. We discuss the challenges in creating a database to hold all relevant and potentially relevant germline information, especially in the light of increased discovery rate through technological advances and improved analysis pipelines. We also reflect on the complexity in handling personalised germline reference sets. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected]  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.  Website of the AIRR-C Germline Database Working Group https://www.antibodysociety.org/the-airr-community/airr-working-groups/germline_database/  Papers mentioned Collins, Andrew M., Mats Ohlin, Martin Corcoran, James M. Heather, Duncan Ralph, Mansun Law, Jesus Martínez-Barnetche, et al. 2023. “AIRR-C Human IG Reference Sets: Curated Sets of Immunoglobulin Heavy and Light Chain Germline Genes.” BioRxiv. https://doi.org/10.1101/2023.09.01.555348  Rodriguez, Oscar L., Yana Safonova, Catherine A. Silver, Kaitlyn Shields, William S. Gibson, Justin T. Kos, David Tieri, et al. 2023. “Genetic Variation in the Immunoglobulin Heavy Chain Locus Shapes the Human Antibody Repertoire.” Nature Communications 14 (1). https://doi.org/10.1038/s41467-023-40070-x  Lees, William D., Scott Christley, Ayelet Peres, Justin T. Kos, Brian Corrie, Duncan Ralph, Felix Breden, et al. 2023. “AIRR Community Curation and Standardised Representation for Immunoglobulin and T Cell Receptor Germline Sets.” Immunoinformatics (Amsterdam, Netherlands) 10 (100025): 100025. https://doi.org/10.1016/j.immuno.2023.100025  Jackson, Katherine J. L., Justin T. Kos, William Lees, William S. Gibson, Melissa Laird Smith, Ayelet Peres, Gur Yaari, et al. 2022. “A BALB/c IGHV Reference Set, Defined by Haplotype Analysis of Long-Read VDJ-C Sequences From F1 (BALB/c x C57BL/6) Mice.” Frontiers in Immunology 13. https://doi.org/10.3389/fimmu.2022.888555  Ford, Easton E., David Tieri, Oscar L. Rodriguez, Nancy J. Francoeur, Juan Soto, Justin T. Kos, Ayelet Peres, et al. 2023. “FLAIRR-Seq: A Method for Single-Molecule Resolution of near Full-Length Antibody H Chain Repertoires.” The Journal of Immunology 210 (10): 1607–19. https://doi.org/10.4049/jimmunol.2200825  Omer, Aviv, Ayelet Peres, Oscar L. Rodriguez, Corey T. Watson, William Lees, Pazit Polak, Andrew M. Collins, and Gur Yaari. 2022. “T Cell Receptor Beta Germline Variability Is Revealed by Inference from Repertoire Data.” Genome Medicine 14 (1). https://doi.org/10.1186/s13073-021-01008-4  Rodriguez, Oscar L., Catherine A. Silver, Kaitlyn Shields, Melissa L. Smith, and Corey T. Watson. 2022. “Targeted Long-Read Sequencing Facilitates Phased Diploid Assembly and Genotyping of the Human T Cell Receptor Alpha, Delta, and Beta Loci.” Cell Genomics 2 (12): 100228. https://doi.org/10.1016/j.xgen.2022.100228  Tools mentioned TIgGER (Immcantation) https://tigger.readthedocs.io/en/stable  IgDiscover https://github.com/NBISweden/IgDiscover  Partis https://github.com/psathyrella/partis MiXCR https://mixcr.com

Alexander Bernier BCL, JD, LLM, SJD (Candidate) is a Montreal-based lawyer, and a doctoral candidate at the University of Toronto Faculty of Law. His work aims to give scientists a range of compliant data sharing designs that scientists can implement in different situations. In this episode, we discuss the risk of identifying individuals in a biological data set, how this is approached differently in different countries, and possible strategies to ensure data privacy. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected]  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. 

Maxim Zaslavsky is a computer scientist using machine learning to address problems in immunology. He is currently PhD student at Stanford University. Scott D. Boyd is a physician-scientist and Professor of Pathology and of Food Allergy and Immunology at Stanford University. His group is focused on using high-throughput DNA sequencing and single-cell experiments to analyse human immune responses to infection and vaccination. We discuss the preprint “Disease diagnostics using machine learning of immune receptors”, available at BioRxiv: https://doi.org/10.1101/2022.04.26.489314. The work is led by Maxim Zaslavsky with Scott Boyd the corresponding author. In the manuscript, the authors demonstrate how AIRR-seq and machine learning can be used in disease diagnostics. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected]  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.

Dr. Charlotte Deane is Professor of Structural Bioinformatics in the Department of Statistics in University of Oxford (UK) and heads the Oxford Protein Informatics Group. Prof. Deane’s research merges statistics, immunoinformatics, protein structure and small molecule drug discovery. Her group has published several databases that are widely used by academic researchers and in pharmaceutical drug discovery pipelines. We discuss the relevance of including protein structure to study and design antibodies, and the availability of such data.  The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.