A team led by Huang Zhiwei, a scientist from Rugao, Nantong, Jiangsu province published a thesis in international journal Molecular Cell that analyzed the molecular mechanism of cholesterol inhibiting T cell receptor (TCR) signaling, marking another discovery in immunology by Chinese scientists.

Huang Zhiwei (second from right) and his team members carry out laboratory research. [Photo/WeChat account: rugaofabu]

The research provides an important scientific basis for the development of immunotherapy based on TCR and the treatment of autoimmune diseases.

T cells are key cells in the adaptive immune system of vertebrates, and TCR plays an important role in viral infections, cancer, and autoimmune diseases.

In 2019, Huang's research team first analyzed the structure of human TCR complex in a thesis published in Nature.

In the past 20 years, TCR has been extensively studied internationally, but the mechanism of its signal transduction is not clear, said Huang.

The thesis published in Molecular Cell analyzed high-resolution cryo-electron microscopy structures of human wild-type, cholesterol-sulfate bound, and constitutively activated TCR-CD3 complexes, revealed the mechanism by which cholesterol restricts TCR activity by capturing the conformation of TCR in the resting and active states, and provided a structural and theoretical basis for understanding the conformational change of TCR from resting state to active state.