| First Author | Iwanami N | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 911 |
| PubMed ID | 36064961 | Mgi Jnum | J:344147 |
| Mgi Id | MGI:7335311 | Doi | 10.1038/s42003-022-03870-3 |
| Citation | Iwanami N, et al. (2022) Clonal dynamics underlying the skewed CD4/CD8 ratio of mouse thymocytes revealed by TCR-independent barcoding. Commun Biol 5(1):911 |
| abstractText | T cell differentiation in the thymus generates CD4(+) helper and cytotoxic CD8(+) cells as the two principal T cell lineages. Curiously, at the end of this complex selection process, CD4(+) cells invariably outnumber CD8(+) cells. Here, we examine the dynamics of repertoire formation and the emergence of the skewed CD4/CD8 ratio using high-resolution endogenous CRISPR/Cas9 barcoding that indelibly marks immature T cells at the DN2/DN3 pre-TCR stage. In wild-type mice, greater clone size of CD4(+) cells and an intrinsically greater probability of Tcr beta clonotypes for pMHCII interactions are major contributors to the skewed CD4/CD8 ratio. Clonal perturbations of thymocyte differentiation following the precocious expression of a rearranged iNKT invariant TCR alpha chain are due to loss of Tcr beta clonotypes from the CD4 lineage-committed pre-selection repertoire. The present barcoding scheme offers a novel means to examine the clonal dynamics of lymphocyte differentiation orthogonal to that using TCR clonotypes. |
