A T cell can have many roles in the immune system. Credit: National Institute of Allergy and Infectious Diseases , T cells have a nuclear receptor doing something very odd—but very important—to help them fight pathogens and destroy cancer cells.
Special molecules called T cell receptors sit on the cell membrane, where they receive messages from other cells. You can imagine TCRs as fire-spotters, the lookouts who scan for smoke from remote cabins in the wilderness. Just as fire-spotters need to alert officials to any smoke in the distance, TCRs need to quickly signal headquarters—the cell nucleus—if they detect a potential threat, such as a virus or cancer cell.
RARα belongs to a large family of retinoic acid receptors that normally sit on control regions of target genes in the nucleus. These retinoic acid receptors recruit repressor and activator molecules that let them"switch off" or"switch on" expression of these target genes. This important job in the nucleus has earned retinoic acid receptors the title of"nuclear receptors.
Could these two isoforms play different roles in T cells? Looking closer, the researchers realized this RARα isoform did not respond to retinoic acid and didn't even have the right equipment to function as a"It didn't have the tools that are important for nuclear receptors, namely the ability to interact with DNA and the ability to translocate from the cytoplasm to the nucleus," says Cheroutre.
As Myers and his colleagues examined their data, they were surprised to spot a phosphorylation event related to RARα. In fact, phosphorylation of RARα began just three minutes into T cell activation."Because this event was that early, our findings suggest that this phosphorylation of RARα is near the T cell receptor—and it has a burst in activity right after the TCR is stimulated," says Myers.
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