Characterization of TCR gene rearrangements during adult murine T cell development

Development of the alpha beta and gamma delta T cell lineages is dependent upon the rearrangement and expression of the TCR alpha and beta or gamma an d delta genes, respectively. Although the timing and sequence of rearrangem ents of the TCR alpha and TCR beta loci in adult murine thymic precursors h as been characterized, no similar information is available for the TCR gamm a and TCR delta loci. In this report, we show that approximately half of th e total TCR delta alleles initiate rearrangements at the CD44(high)CD25(+) stage, whereas the TCR beta locus is mainly in germline configuration. In t he subsequent CD44(low)CD25(+) stage, most TCR delta alleles are fully reco mbined, whereas TCR beta rearrangements are only complete on 10-30% of alle les, These results indicate that rearrangement at the TCR delta locus can p recede that of TCR beta locus recombination by one developmental stage. In addition, we find a bias toward productive rearrangements of both TCR delta and TCR gamma genes among CD44(high)CD25(+) thymocytes, suggesting that fu nctional gamma delta TCR complexes can be formed before the rearrangement o f TCR beta, These data support a model of lineage commitment in which seque ntial TCR gene rearrangements may influence alpha beta/gamma delta lineage decisions. Further, because TCR gene rearrangements are generally limited t o T lineage cells, these analyses provide molecular evidence that irreversi ble commitment to the T lineage can occur as early as the CD44(high)CD25(+) stage of development.