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Allelic exclusion of TCR α-chains upon severe restriction of Vα repertoire

Academic Article
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Overview

related to degree

  • Westernberg, Luise Sternberg, Ph.D. in Immunology, Scripps Research 2007 - 2013

authors

  • Rybakin, V.
  • Westernberg, Luise Sternberg
  • Fu, G.
  • Kim, H. O.
  • Ampudia, J.
  • Sauer, Karsten
  • Gascoigne, Nicholas

publication date

  • December 2014

journal

  • PLoS One  Journal

abstract

  • Development of thymocytes through the positive selection checkpoint requires the rearrangement and expression of a suitable T cell receptor (TCR) α-chain that can pair with the already-expressed β-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 α-chain continue to rearrange until a positively-selectable heterodimer is formed, thymocytes and T cells can in principle express dual α-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 β-chain and for two unrearranged α-chains on a genetic background where endogenous α-chains could not be rearranged. Both Vα3.2 and Vα2 containing α-chains were efficiently positively selected, to the extent that a population of dual α-chain-bearing cells was not distinguishable from single α-chain-expressors. Surprisingly, Vα3.2-expressing cells were much more frequent than the Vα2 transgene-expressing cells, even though this Vα3.2-Vβ5 combination can reconstitute a known selectable TCR. In accord with previous work on the Vα3 repertoire, T cells bearing Vα3.2 expressed from the rearranged minilocus were predominantly selected into the CD8+ T cell subpopulation. Because of the dominance of Vα3.2 expression over Vα2 expressed from the miniloci, the peripheral T cell population was predominantly CD8+ cells.

subject areas

  • Alleles
  • Animals
  • CD8-Positive T-Lymphocytes
  • Gene Expression Regulation
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Genetic Loci
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta
  • Thymocytes
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Identity

PubMed Central ID

  • PMC4264757

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0114320

PubMed ID

  • 25500569
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Additional Document Info

volume

  • 9

issue

  • 12

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