RESTORATION OF T-CELL DEVELOPMENT IN RAG-2 DEFICIENT MICE BY FUNCTIONAL TCR TRANSGENES

Introduction of TCRalpha transgene, TCRbeta transgene, or both into RAG-2-/- mice differentially rescues T cell development. RAG-2-/- mice have small numbers of TCR-CD4-CD8- (double negative, DN) thymocytes that express CD3gammadeltaepsilon and zeta proteins intracellularly. Introduction of a TCRbeta transgene, but not a TCRalpha transgene, into the RAG-2-/- background restored normal numbers of thymocytes. These cells were CD4+CD8+ (double positive, DP) and expressed small amounts of surface TCRbeta chain dimers in association with CD3gammadeltaepsilon but not zeta. RAG-2-/- mice that expressed alpha and beta TCR transgenes developed both DP and single positive thymocytes. Thus, the TCRbeta subunit, possibly in association with a novel CD3 complex, participates in the DN to the DP transition.