T Cell Receptor γ Gene Regulatory Sequences Prevent the Function of a Novel TCRγ/pTα Pre–T Cell Receptor

Expression of a TCRγ transgene in RAG-1 −/− mice resulted in the development of a limited number of CD4 + CD8 + (DP) thymocytes. In vivo treatments with anti-TCRγ antibody enhanced the number of DP thymocytes, demonstrating that TCRγ chains were expressed on the cell surface in the absence of δ, α, or β chains. Mutations in pTα or CD3e genes abolished transgene-induced DP cell development, indicating that TCRγ can associate with pTα and CD3 to form a novel pre-TCR. With a transgene containing additional regulatory sequences, TCRγ expression was down-regulated in DP cells, and little DP cell development occurred. Thus, the function of the endogenous TCRγ/pTα is limited by the transcriptional down-regulation of TCRγ genes that normally accompanies DP cell development.