Clone JD3 recognizes the human DR3 antigen, a member of the TNF-receptor superfamily which is also known as tumor necrosis factor receptor superfamily member 25 (TNFRSF25). DR3 is the receptor for TNFSF12 (APO3L, TWEAK) and interacts directly with the adapter TRADD. It mediates activation of NFκB and induces apoptosis. DR3 is expressed preferentially by activated and antigen-experienced T lymphocytes. It is also highly expressed by FoxP3-positive regulatory T lymphocytes. DR3 is activated by TNFSF15, which is rapidly upregulated in antigen-presenting cells and some endothelial cells following toll-like receptor or Fc receptor activation. Multiple alternatively spliced transcript variants of this gene-encoding distinct isoforms have been reported, most of which are potentially secreted molecules. The alternative splicing of DR3 in B and T cells encounters a programmed change upon T cell–activation, which predominantly produces full-length, membrane-bound isoforms, and is thought to be involved in controlling lymphocyte proliferation induced by T cell–activation. DR3 stimulation is therefore highly specific to T cell–mediated immunity, which can be used to enhance or dampen inflammation depending on the temporal context and quality of foreign versus self antigen availability. Stimulation of DR3 in humans leads to similar effects as costimulatory blockade targeting molecules such as CTLA-4 and PD-1.