How the T cell receptor starts immune attacks ^{CEFR B2}

Scientists led from the Laboratory of Molecular Electron Microscopy used cryo-EM to image the T cell receptor (TCR) inside a biochemical environment that mimicked its native membrane. The study, published in Nature Communications, reported a closed, compacted receptor in the resting state that opens and extends when it meets an antigen-presenting molecule, a change the authors liken to a jack-in-the-box.

Two methodological changes made this view possible. First, the team reconstituted the multi-protein TCR complex into nanodiscs — small disc-shaped membrane patches stabilised by a scaffold protein — which required assembling all eight proteins correctly and proved technically challenging. Second, they used a lipid mixture chosen to resemble the native T cell membrane. By contrast, earlier structural work used detergent, which removes the membrane and apparently allowed the receptor to appear open even when dormant.

The authors argue that seeing the intact, membrane-held TCR offers new avenues to refine and broaden T cell immunotherapies. They propose that receptor sensitivity might be re-engineered and activation thresholds tuned for adoptive T cell therapies used in some rare sarcomas. The structures could also inform vaccine design and enable detailed study of interactions between HLA-presented antigens and T cell receptors.