How compartmentalization and proliferation shape the splenic T cell repertoire during an immune response to a complex antigen in mice
- 1Data Science Group, Institute for Computing and Information Sciences, Radboud University, Nijmegen, The Netherlands.
- 2Institut für Anatomie, Universität zu Lübeck, Lübeck, Germany.
- 3Medical BioSciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Abstract
The adaptive immune system recognizes billions of unique antigens using highly variable T cell receptors (TCRs). To what extent TCR features shape the spatial distribution of the TCR repertoire (TCR-R) within lymphoid organs remains unclear. Here, we compared the TCR-R composition in T cell zones (TCZ), B cell zones (BCZ), and germinal centers (GC) of the spleen by analyzing the complementarity-determining region 3 of the beta chain (CDR3β) in microdissected splenic compartments from naïve and immunized mice. While we found substantial differences in TCR-R composition between these compartments, these differences largely disappeared once the effects of compartment size and proliferation were accounted for: During steady state, the few T cells found in BCZs strongly resemble random subsets of those found in TCZs. After immunization, expanded clones started appearing in the TCZ at day 3 and later shifted to the BCZ. GCs harbored even further expanded clones that were grouped into clusters with high sequence similarity. TCR-R differences during the immune response were well explained by a Galton-Watson model of T cell proliferation, suggesting that this could be the central factor shaping the observed TCR-R differences. Similarly, while TCR length and closeness to germline initially showed more pronounced differences between the compartments, our models of random distribution and proliferation explained these differences almost entirely. Hence, our findings suggest that splenic TCR-Rs are shaped predominantly by compartment size and proliferation rates rather than TCR sequence features. This would imply that quantitative assessment of TCR-R dynamics across heterogeneous spatial compartments during an immune response is only possible when these effects are explicitly accounted for. Author summary: T cells are an integral part of the adaptive immune system, working with B cells to detect and remove infectious and cancerous cells. To do this, they have receptors that recognize small peptides (antigens) presented by other cells. The immune system has a large repertoire of T cell receptors (TCRs). During an immune response, cells that recognize an antigen expand.
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BibTeX
@article{buytenhuijs2026compartmentalization,
title = {{How compartmentalization and proliferation shape the splenic T cell repertoire during an immune response to a complex antigen in mice}},
author = {Franka Buytenhuijs and Cornelia Tune and Thomas C Smits and Andrea Schampel and Lisa-Kristin Schierloh and René Pagel and Jürgen Westermann and Johannes Textor},
journal = {PLOS Computational Biology},
year = {2026},
month = oct,
doi = {10.1371/journal.pcbi.1014859},
url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014859},
note = {CC BY},
}
RIS
TY - JOUR
TI - How compartmentalization and proliferation shape the splenic T cell repertoire during an immune response to a complex antigen in mice
AU - Franka Buytenhuijs
AU - Cornelia Tune
AU - Thomas C Smits
AU - Andrea Schampel
AU - Lisa-Kristin Schierloh
AU - René Pagel
AU - Jürgen Westermann
AU - Johannes Textor
PY - 2026
DA - 2026/10/14
JO - PLOS Computational Biology
DO - 10.1371/journal.pcbi.1014859
UR - https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014859
AB - The adaptive immune system recognizes billions of unique antigens using highly variable T cell receptors (TCRs). To what extent TCR features shape the spatial distribution of the TCR repertoire (TCR-R) within lymphoid organs remains unclear. Here, we compared the TCR-R composition in T cell zones (TCZ), B cell zones (BCZ), and germinal centers (GC) of the spleen by analyzing the complementarity-determining region 3 of the beta chain (CDR3β) in microdissected splenic compartments from naïve and immunized mice. While we found substantial differences in TCR-R composition between these compartments, these differences largely disappeared once the effects of compartment size and proliferation were accounted for: During steady state, the few T cells found in BCZs strongly resemble random subsets of those found in TCZs. After immunization, expanded clones started appearing in the TCZ at day 3 and later shifted to the BCZ. GCs harbored even further expanded clones that were grouped into clusters with high sequence similarity. TCR-R differences during the immune response were well explained by a Galton-Watson model of T cell proliferation, suggesting that this could be the central factor shaping the observed TCR-R differences. Similarly, while TCR length and closeness to germline initially showed more pronounced differences between the compartments, our models of random distribution and proliferation explained these differences almost entirely. Hence, our findings suggest that splenic TCR-Rs are shaped predominantly by compartment size and proliferation rates rather than TCR sequence features. This would imply that quantitative assessment of TCR-R dynamics across heterogeneous spatial compartments during an immune response is only possible when these effects are explicitly accounted for. Author summary: T cells are an integral part of the adaptive immune system, working with B cells to detect and remove infectious and cancerous cells. To do this, they have receptors that recognize small peptides (antigens) presented by other cells. The immune system has a large repertoire of T cell receptors (TCRs). During an immune response, cells that recognize an antigen expand.
SN - 1553-7358
SN - 1553-734X
ER -