The tight interallelic positional coincidence that distinguishes T-cell receptor Jα usage does not result from homologous chromosomal pairing during VαJα rearrangement

The T-cell receptor (TCR) α locus is thought to undergo multiple cycles of secondary rearrangements that maximize the generation of αβ T cells. Taking advantage of the nucleotide sequence of the human Vα and Jα segments, we undertook a locus-wide analysis of TCRα gene rearrangements in human αβ T-cell clones. In most clones, VαJα rearrangements occurred on both homologous chromosomes and, remarkably, resulted in the use of two neighboring Jα segments. No such interallelic coincidence was found for the position of the two rearranged Vα segments, and there was only a loose correlation between the 5′ or 3′ chromosomal position of the Vα and Jα segments used in a given rearrangement. These observations question the occurrence of extensive rounds of secondary Vα→Jα rearrangements and of a coordinated and polarized usage of the Vα and Jα libraries. Fluorescence in situ hybridization analysis of developing T cells in which TCRα rearrangements are taking place showed that the interallelic positional coincidence in Jα usage cannot be explained by the stable juxtaposition of homologous Jα clusters.