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) 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.