Microbiome Shapes the T Cell Receptor Repertoire among CD4+CD8+ Thymocytes
2022
Sherri L. Surman | Jeremy Crawford | Pradyot Dash | Susan L. Tonkonogy | Paul G. Thomas | Julia L. Hurwitz
The microbiome shapes the mature T cell receptor (TCR) repertoire and thereby influences pathogen control. To investigate microbiome influences on T cells at an earlier, immature stage, we compared single-cell TCR transcript sequences between CD4+CD8+ (double-positive) thymocytes from gnotobiotic [<i>E. coli</i> mono-associated (Ec)] and germ-free (GF) mice. Identical TCRβ transcripts (termed repeat, REP) were more often shared between cells of individual Ec mice compared to GF mice (Fishers Exact test, <i>p</i> < 0.0001). Among Ec REPs, a cluster of Vβ genes (Vβ12-1, 12-2, 13-1, and 13-2, termed 12-13) was well represented, whereas 12-13 sequences were not detected among GF REPs (Fishers Exact test, <i>p</i> = 0.046). Vα genes located in the distal region of the TCRα locus were more frequently expressed in Ec mice compared to GF mice, both among REPs and total sequences (Fishers Exact test, <i>p</i> = 0.009). Results illustrate how gut bacteria shape the TCR repertoire, not simply among mature T cells, but among immature CD4+CD8+ thymocytes.
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