| First Author | Rybakin V | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 12 | Pages | e114320 |
| PubMed ID | 25500569 | Mgi Jnum | J:225123 |
| Mgi Id | MGI:5691606 | Doi | 10.1371/journal.pone.0114320 |
| Citation | Rybakin V, et al. (2014) Allelic exclusion of TCR alpha-chains upon severe restriction of Valpha repertoire. PLoS One 9(12):e114320 |
| abstractText | Development of thymocytes through the positive selection checkpoint requires the rearrangement and expression of a suitable T cell receptor (TCR) alpha-chain that can pair with the already-expressed beta-chain to make a TCR that is selectable. That is, it must have sufficient affinity for self MHC-peptide to induce the signals required for differentiation, but not too strong so as to induce cell death. Because both alleles of the alpha-chain continue to rearrange until a positively-selectable heterodimer is formed, thymocytes and T cells can in principle express dual alpha-chains. However, cell-surface expression of two TCRs is comparatively rare in mature T cells because of post-transcriptional regulatory mechanisms termed "phenotypic allelic exclusion". We produced mice transgenic for a rearranged beta-chain and for two unrearranged alpha-chains on a genetic background where endogenous alpha-chains could not be rearranged. Both Valpha3.2 and Valpha2 containing alpha-chains were efficiently positively selected, to the extent that a population of dual alpha-chain-bearing cells was not distinguishable from single alpha-chain-expressors. Surprisingly, Valpha3.2-expressing cells were much more frequent than the Valpha2 transgene-expressing cells, even though this Valpha3.2-Vbeta5 combination can reconstitute a known selectable TCR. In accord with previous work on the Valpha3 repertoire, T cells bearing Valpha3.2 expressed from the rearranged minilocus were predominantly selected into the CD8+ T cell subpopulation. Because of the dominance of Valpha3.2 expression over Valpha2 expressed from the miniloci, the peripheral T cell population was predominantly CD8+ cells. |
