T-CELL RECEPTOR-GAMMA GENE REGULATORY SEQUENCES PREVENT THE FUNCTION OF A NOVEL TCR-GAMMA PT-ALPHA PRE-T CELL-RECEPTOR/

Expression of a TCR gamma transgene in RAG-1(-/-) mice resulted in the development of a limited number of CD4(+)CD8(+) (DP) thymocytes. In v ivo treatments with anti-TCR gamma antibody enhanced the number of DP thymocytes, demonstrating that TCR gamma chains were expressed on the cell surface in the absence of delta, alpha, or beta chains. Mutations in pT alpha or CD3 epsilon genes abolished transgene-induced DP cell development, indicating that TCR gamma can associate with pT alpha and CD3 to form a novel pre-TCR. With a transgene containing additional r egulatory sequences, TCR gamma expression was downregulated in DP cell s, and little DP cell development occurred. Thus, the function of the endogenous TCR gamma/pT alpha is limited by the transcriptional down-r egulation of TCR gamma genes that normally accompanies DP cell develop ment.