科研之友
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摘要
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 V alpha 3.2 and V alpha 2 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, V alpha 3.2-expressing cells were much more frequent than the V alpha 2 transgene-expressing cells, even though this V alpha 3.2-V beta 5 combination can reconstitute a known selectable TCR. In accord with previous work on the V alpha 3 repertoire, T cells bearing V alpha 3.2 expressed from the rearranged minilocus were predominantly selected into the CD8(+) T cell subpopulation. Because of the dominance of V alpha 3.2 expression over V alpha 2 expressed from the miniloci, the peripheral T cell population was predominantly CD8(+) cells.
- 出版日期2014-12-12
