RT Journal Article
SR Electronic
T1 Deep Sequencing Reveals Transient Segregation of T Cell Repertoires in Splenic T Cell Zones During an Immune Response
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 229013
DO 10.1101/229013
A1 J. Textor
A1 A. Fähnrich
A1 M. Meinhardt
A1 C. Tune
A1 S. Klein
A1 R. Pagel
A1 P. König
A1 K. Kalies
A1 J. Westermann
YR 2017
UL http://biorxiv.org/content/early/2017/12/08/229013.abstract
AB 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 naïve 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 β 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.