T cell receptor gamma gene regulatory sequences prevent the function of a novel TCRgamma/pTalpha pre-T cell receptor.

Expression of a TCRgamma transgene in RAG-1-/- mice resulted in the development of a limited number of CD4+CD8+ (DP) thymocytes. In vivo treatments with anti-TCRgamma antibody enhanced the number of DP thymocytes, demonstrating that TCRgamma chains were expressed on the cell surface in the absence of delta, alpha, or beta chains. Mutations in pTalpha or CD3epsilon genes abolished transgene-induced DP cell development, indicating that TCRgamma can associate with pTalpha and CD3 to form a novel pre-TCR. With a transgene containing additional regulatory sequences, TCRgamma expression was down-regulated in DP cells, and little DP cell development occurred. Thus, the function of the endogenous TCRgamma/pTalpha is limited by the transcriptional down-regulation of TCRgamma genes that normally accompanies DP cell development.