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J Immunol. 2018 Jul 15;201(2):350-358. doi: 10.4049/jimmunol.1800091. Epub 2018 Jun 8.

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

Author information

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; and.
2
Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University of Lübeck, 23538 Lübeck, Germany.
3
Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University of Lübeck, 23538 Lübeck, Germany westermann@anat.uni-luebeck.de.

Abstract

Immunological differences between hosts, such as diverse 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 microenvironmental niches. By harboring distinct TCRs, such niches could enhance within-host immunological diversity. In contrast, rapid T cell migration is expected to dilute such diversity. In this study, we combined tissue microdissection and deep sequencing of the TCR β-chain to examine the extent to which TCR repertoires differ between TCZs in murine spleens. In the absence of Ag, we found little evidence for differences between TCZs of the same spleen. Yet, 3 d after immunization with sheep RBCs, 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 d after immunization, when hallmarks of an ongoing immune response were still observed. These data suggest that in the absence of Ag, any repertoire differences observed between TCZs of the same host can largely be attributed to random clone distribution. Upon Ag challenge, TCR repertoires in TCZs first segregate and then homogenize within days. Such "transient mosaic" dynamics could be an important barrier for pathogen adaptation and spread during an immune response.

PMID:
29884700
DOI:
10.4049/jimmunol.1800091

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