Allelic Exclusion of TCR α-Chains upon Severe Restriction of Vα Repertoire

摘要: Development of thymocytes through the positive selection checkpoint requires rearrangement and expression a suitable T cell receptor (TCR) α-chain that can pair with already-expressed β-chain to make TCR is selectable. That is, it must have sufficient affinity for self MHC-peptide induce signals required differentiation, but not too strong so as death. Because both alleles continue rearrange until positively-selectable heterodimer formed, cells in principle express dual α-chains. However, cell-surface two TCRs comparatively rare mature because post-transcriptional regulatory mechanisms termed "phenotypic allelic exclusion". We produced mice transgenic rearranged unrearranged α-chains on genetic background where endogenous could be rearranged. Both Vα3.2 Vα2 containing were efficiently positively selected, extent population α-chain-bearing was distinguishable from single α-chain-expressors. Surprisingly, Vα3.2-expressing much more frequent than transgene-expressing cells, even though this Vα3.2-Vβ5 combination reconstitute known selectable TCR. In accord previous work Vα3 repertoire, bearing expressed minilocus predominantly selected into CD8+ subpopulation. dominance over miniloci, peripheral cells.