Biology subjects

Textor, J.

Publications and source records attributed to Textor, J..

4 recordsLinked to original sources

bioRxiv2018

Robust self-nonself discrimination requires negative T cell selection on non-random peptides

Self-foreign discrimination by the immune system was long thought to arise because negative selection in the thymus silences self-reactive T cells. Yet recent data show that this silencing is remarkably incomplete. Here we ask how a repertoire containing many self-reactive cells can nevertheless discriminate self from foreign. We address this question using realistic-scale computational models of the T cell repertoire. Our models show that when foreign peptides dif-fer systematically from self, moderate T cell cross-reactivity skews the post-selection repertoire towards foreign recognition. When no such systematic differences exist, self-foreign discrim-ination is only possible if peptide presentation in the thymus minimizes the co-occurrence of similar, redundant self peptides. These results imply that negative selection needs to be based on non-random self peptides to allow robust self-foreign discrimination for both self-similar and -dissimilar pathogens.

immunology↗

bioRxiv2018

Local Attachment Explains Small-World-Like Properties of Fibroblastic Reticular Cell Networks in Lymph Nodes

Fibroblastic reticular cells (FRCs) form a cellular network that serves as the structural backbone of lymph nodes and facilitates lymphocyte migration. This FRC network has been found to have small-world properties. Using a model based on geographical preferential attachment, we simulated the formation of a variety of cellular networks and show that similar small-world properties robustly emerge under such natural conditions. By estimating the parameters of this model, we generated FRC network representations with realistic topological properties. We found that these properties change markedly when the network is expanded from a thin slice to a 3D cube. Typical small-world properties were found to persist as network size was increased. The simulated networks were very similar to 2D and 3D lattice networks. According to the used metrics, these lattice networks also have small-world properties, indicating that lattice-likeness is sufficient to become classified as a small-world network. Our results explain why FRC networks have small-world properties and provide a framework for simulating realistic FRC networks.

immunology↗

bioRxiv2018

Both cell-intrinsic and environmental factors constrain speed and persistence in T cell migration

Cell migration is astoundingly diverse. Molecular signatures, cell-cell and cell-matrix interactions, and environmental structures each play their part in shaping cell motion, yielding numerous different cell morphologies and migration modes. Nevertheless, in recent years, a simple unifying law was found to describe cell migration across many different cell types and contexts: faster cells turn less frequently. Given this universal coupling between speed and persistence (UCSP), from a modelling perspective it is important to know whether computational models of cell migration capture this speed-persistence link. Here, we present an in-depth characterisation of an existing Cellular Potts Model (CPM). We first show that this model robustly reproduces the UCSP without having been designed for this task. Instead, we show that this fundamental law of migration emerges spontaneously through a crosstalk of intracellular mechanisms, cell shape, and environmental constraints, resembling the dynamic nature of cell migration in vivo. Our model also reveals how cell shape dynamics can further constrain cell motility by limiting both the speed and persistence a cell can reach, and how a rigid environment such as the skin can restrict cell motility even further. Our results further validate the CPM as a model of cell migration, and shed new light on the speed-persistence coupling that has emerged as a fundamental property of migrating cells. SIGNIFICANCEThe universal coupling between speed and persistence (UCSP) is the first general quantitative law describing motility patterns across the versatile spectrum of migrating cells. Here, we show - for the first time - that this migration law emerges spontaneously in an existing, highly popular computational model of cell migration. Studying the UCSP in entirely different model frameworks, not explicitly built with this law in mind, can help uncover how intracellular dynamics, cell shape, and environment interact to produce the diverse motility patterns observed in migrating cells.

immunology↗

bioRxiv2017

Deep Sequencing Reveals Transient Segregation of T Cell Repertoires in Splenic T Cell Zones During an Immune Response

Immunological differences between hosts, such as diverse T-cell receptor (TCR) repertoires, are widely credited for reducing the risk of pathogen spread and adaptation in a population. Within-host immunological diversity might likewise be important for robust pathogen control, but to what extent naive TCR repertoires differ across different locations in the same host is unclear. T-cell zones (TCZs) in secondary lymphoid organs provide secluded micro-environmental niches. By harboring distinct TCRs, such niches could enhance within-host immunological diversity. On the other hand, rapid T cell migration is expected to dilute such diversity. Here, we combined tissue micro-dissection and deep sequencing of the TCR {beta} chain to examine the extent to which TCR repertoires differ between TCZs in murine spleens. In the absence of antigen, we found little evidence for differences between different TCZs of the same spleen. Yet, three days after immunization with sheep red blood cells, we observed a >10-fold rise in the number of clones that appeared to localize to individual zones. Remarkably, these differences largely disappeared at 4 days after immunization, when hallmarks of an ongoing immune response were still observed. These data suggest that in the absence of antigen, any repertoire differences observed between TCZs of the same host can largely be attributed to random clone distribution. Upon antigen challenge, segregated TCR compartments appear and disappear within days. Such \"transient mosaic\" dynamics could be an important barrier for pathogen adaptation and spread during an immune response.

immunology↗