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,§
*
Section of Immunobiology and
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520; and
Memorial Sloan Kettering Cancer Center and
§
Cornell University Graduate School of Medical Sciences, New York, NY 10021
Development of the 
ß and 
T cell lineages is dependent
upon the rearrangement and expression of the TCR and ß or and
genes, respectively. Although the timing and sequence of
rearrangements of the TCR and TCRß loci in adult murine thymic
precursors has been characterized, no similar information is available
for the TCR and TCR loci. In this report, we show that
approximately half of the total TCR alleles initiate rearrangements
at the CD44highCD25+ stage, whereas the
TCRß locus is mainly in germline configuration. In the subsequent
CD44lowCD25+ stage, most TCR alleles are
fully recombined, whereas TCRß rearrangements are only complete on
10–30% of alleles. These results indicate that rearrangement at the
TCR locus can precede that of TCRß locus recombination by one
developmental stage. In addition, we find a bias toward productive
rearrangements of both TCR and TCR genes among
CD44highCD25+ thymocytes, suggesting that
functional TCR complexes can be formed before the rearrangement
of TCRß. These data support a model of lineage commitment in which
sequential TCR gene rearrangements may influence ß/ lineage
decisions. Further, because TCR gene rearrangements are generally
limited to T lineage cells, these analyses provide molecular evidence
that irreversible commitment to the T lineage can occur as early as the
CD44highCD25+ stage of
development.
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