More efficient positive selection of thymocytes in mice lacking terminal deoxynucleotidyl transferase

Mice with a drastic mutation in the terminal deoxynucleotidyl transferase (TdT) gene have recently been engineered. Igs and TCRs in these mice are essentially devoid of N-region diversity. Here we report that TdT0 mice contain elevated numbers of CD3hi single-positive (SP) thymocytes because more thymocytes make the transition from the immature double-positive to the mature SP stage. This suggests that the repertoire of TCRs encoded in the germline may be enriched for specificities capable of interacting with MHC molecules and that the loss of some of this affinity is the price paid for TdT-generated diversity.