Identification of a Putative Regulator of Early T Cell Activation Genes

TLDR

NFAT‑1, a protein that binds the HIV‑1 LTR, is known to be stimulated during early T‑cell activation. The study aimed to identify molecules regulating early T‑cell activation genes by examining the IL‑2 enhancer. Functional sequences of the IL‑2 enhancer were used to probe antigen‑receptor‑dependent regulation. NFAT‑1 rapidly forms a complex with activated T‑cell nuclear extracts, appears 10–25 min before IL‑2 activation, and its binding site drives promoter activity only in antigen‑activated T cells, indicating NFAT‑1 transmits signals from the T‑cell receptor.

Abstract

Molecules involved in the antigen receptor-dependent regulation of early T cell activation genes were investigated with the use of functional sequences of the T cell activation-specific enhancer of interleukin-2 (IL-2). One of these sequences forms a protein complex, NFAT-1, specifically with nuclear extracts of activated T cells. This complex appeared 10 to 25 minutes before the activation of the IL-2 gene. Studies with inhibitors of protein synthesis indicated that the time of synthesis of the activator of the IL-2 gene in Jurkat T cells corresponds to the time of appearance of NFAT-1. NFAT-1, or a very similar protein, bound functional sequences of the long terminal repeat (LTR) of the human immunodeficiency virus type 1; the LTR of this virus is known to be stimulated during early T cell activation. The binding site for this complex activated a linked promoter after transfection into antigen receptor-activated T cells but not other cell types. These characteristics suggest that NFAT-1 transmits signals initiated at the T cell antigen receptor.