Predicting T cell receptor functionality against mutant epitopes

Drost F, Dorigatti E, Straub A, Hilgendorf P, Wagner KI, Heyer K, López Montes M, Bischl B, Busch DH, Schober K, Schubert B (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cell Genomics Elsevier

Article Number: 100634

DOI: 10.1016/j.xgen.2024.100634

Abstract

Cancer cells and pathogens can evade T cell receptors (TCRs) via mutations in immunogenic epitopes. TCR cross-reactivity (i.e., recognition of multiple epitopes with sequence similarities) can counteract such escape but may cause severe side effects in cell-based immunotherapies through targeting self-antigens. To predict the effect of epitope point mutations on T cell functionality, we here present the random forest-based model Predicting T Cell Epitope-Specific Activation against Mutant Versions (P-TEAM). P-TEAM was trained and tested on three datasets with TCR responses to single-amino-acid mutations of the model epitope SIINFEKL, the tumor neo-epitope VPSVWRSSL, and the human cytomegalovirus antigen NLVPMVATV, totaling 9,690 unique TCR-epitope interactions. P-TEAM was able to accurately classify T cell reactivities and quantitatively predict T cell functionalities for unobserved single-point mutations and unseen TCRs. Overall, P-TEAM provides an effective computational tool to study T cell responses against mutated epitopes.

Authors with CRIS profile

Philipp Hilgendorf Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Drost, F., Dorigatti, E., Straub, A., Hilgendorf, P., Wagner, K.I., Heyer, K.,... Schubert, B. (2024). Predicting T cell receptor functionality against mutant epitopes. Cell Genomics. https://doi.org/10.1016/j.xgen.2024.100634

MLA:

Drost, Felix, et al. "Predicting T cell receptor functionality against mutant epitopes." Cell Genomics (2024).

BibTeX: Download