Identification of a T-cell-specific enhancer at the locus encoding T-cell antigen receptor gamma chain.

作者：Dietmar J. Kappes, Carol Browne, Susumu Tonegawa · 发表于：Proceedings of the National Academy of Sciences · 年份：1991 · DOI：10.1073/pnas.88.6.2204 · 被引用次数：42 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、CAR-T cell therapy research

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.