Vujović, Milena;
Marcatili, Paolo;
Chain, Benny;
Kaplinsky, Joseph;
Andresen, Thomas Lars;
(2023)
Signatures of T cell immunity revealed using sequence similarity with TCRDivER algorithm.
Communications Biology
, 6
(1)
, Article 357. 10.1038/s42003-023-04702-8.
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Abstract
Changes in the T cell receptor (TCR) repertoires have become important markers for monitoring disease or therapy progression. With the rise of immunotherapy usage in cancer, infectious and autoimmune disease, accurate assessment and comparison of the "state" of the TCR repertoire has become paramount. One important driver of change within the repertoire is T cell proliferation following immunisation. A way of monitoring this is by investigating large clones of individual T cells believed to bind epitopes connected to the disease. However, as a single target can be bound by many different TCRs, monitoring individual clones cannot fully account for T cell cross-reactivity. Moreover, T cells responding to the same target often exhibit higher sequence similarity, which highlights the importance of accounting for TCR similarity within the repertoire. This complexity of binding relationships between a TCR and its target convolutes comparison of immune responses between individuals or comparisons of TCR repertoires at different timepoints. Here we propose TCRDivER algorithm (T cell Receptor Diversity Estimates for Repertoires), a global method of T cell repertoire comparison using diversity profiles sensitive to both clone size and sequence similarity. This approach allowed for distinction between spleen TCR repertoires of immunised and non-immunised mice, showing the need for including both facets of repertoire changes simultaneously. The analysis revealed biologically interpretable relationships between sequence similarity and clonality. These aid in understanding differences and separation of repertoires stemming from different biological context. With the rise of availability of sequencing data we expect our tool to find broad usage in clinical and research applications.
| Type: | Article |
|---|---|
| Title: | Signatures of T cell immunity revealed using sequence similarity with TCRDivER algorithm |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s42003-023-04702-8 |
| Publisher version: | https://doi.org/10.1038/s42003-023-04702-8 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Mice, Animals, T-Lymphocytes, Receptors, Antigen, T-Cell, Immunization, Immunotherapy, Algorithms |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10168372 |
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