Journal
EMBO JOURNAL
Volume 20, Issue 17, Pages 4717-4729Publisher
WILEY
DOI: 10.1093/emboj/20.17.4717
Keywords
DNA recombination; homologous chromosomal pairing; T cell; T-cell receptor; V alpha repertoire
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Funding
- Intramural NIH HHS [Z99 CA999999] Funding Source: Medline
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The T-cell receptor (TCR) a locus is thought to undergo multiple cycles of secondary rearrangements that maximize the generation of alpha beta T cells. Taking advantage of the nucleotide sequence of the human V alpha and J alpha segments, we undertook a locus-wide analysis of TCR alpha gene rearrangements in human alpha beta T-cell clones. In most clones, V alphaJ alpha rearrangements occurred on both homologous chromosomes and, remarkably, resulted in the use of two neighboring J alpha segments. No such interallelic coincidence was found for the position of the two rearranged V alpha segments, and there was only a loose correlation between the 5' or 3' chromosomal position of the V alpha and J alpha segments used in a given rearrangement. These observations question the occurrence of extensive rounds of secondary V alpha-->J alpha rearrangements and of a coordinated and polarized usage of the V alpha and J alpha libraries. Fluorescence in situ hybridization analysis of developing T cells in which TCR alpha rearrangements are taking place showed that the interallelic positional coincidence in J alpha usage cannot be explained by the stable juxtaposition of homologous J alpha clusters.
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