IDENTIFICATION OF A T-CELL-SPECIFIC ENHANCER AT THE LOCUS ENCODING T-CELL ANTIGEN RECEPTOR-GAMMA CHAIN

The gamma-delta and alpha-beta-T-cell antigen receptor (TCR) heterodimers are expressed in a lineage-specific, mutually exclusive manner. Regulation of expression occurs at the transcriptional level. A 13-kilobase (kb) stretch of DNA encompassing variable-joining-constant segments V-gamma-4-J-gamma-1-C-gamma-1 of the murine gamma-chain gene was examined for the presence of transcriptional enhancing elements by a transient transfection assay. DNA fragments from this region were inserted into a test plasmid containing a heterologous promoter fused to the human growth hormone gene. An 1800-base-pair (bp) fragment located 3 kb 3' to C-gamma exon III was found to display enhancing activity in several T-cell lines. Maximum enhancing activity could be localized further to fragments as small as 400 bp in some cell lines. Nucleotide sequence analysis of this 400-bp segment revealed homologies to previously described core enhancer elements and to other TCR gene enhancers. The TCR gamma-chain gene enhancer is active in both gamma-delta and alpha-beta T cells, indicating that it is not primarily responsible for lineage-specificity of expression, but it is inactive in non-T-cells.