V alpha gene replacement in a TCR alpha knock-in mouse

Using a TCR alpha chain knock-in mouse, we demonstrate that V-gene replacem ent can operate in the T cell receptor alpha locus. Functional TCR alpha ch ain transcripts generated by V alpha -gene replacement at the site of the V alpha -embedded heptamer were identified in splenic T cells. This finding shows that V alpha -gene replacement can likely be used to shape the periph eral T cell repertoire. The conservation of the embedded heptamer in most V alpha segments adds support to the notion that V-gene replacement is a mec hanism maintained to diversify the immune system and that argues that it is common to B and T cells.