TCR-BETA AND TCR-ALPHA GENE ENHANCERS CONFER TISSUE-SPECIFICITY AND STAGE-SPECIFICITY ON V(D)J RECOMBINATION EVENTS

We describe transgenic mice carrying germline variable gene segments associated with either the T cell receptor (TCR) beta or alpha gene enhancers (Ebeta or Ealpha). Transgenic constructs underwent high rates of site-specific rearrangements predominantly in T cells from independent mice. Rearrangements of the Ebeta-containing transgenes began at different stages of T cell differentiation in embryonic and adult thymus than did the Ealpha-containing ones, with a pattern superimposable upon the patterns of TCRbeta or TCRalpha gene expression, respectively. We demonstrate that sequences within the TCRbeta and TCRalpha gene enhancers confer tissue- and stage-specificity upon the V(D)J recombination events affecting adjacent gene segments. The patterns of transgene expression also gave information on developmental events and lineage relationships (gammadelta versus alphabeta) during T cell development.