The immune system is composed of many interdependent cell types that collectively protect the body from bacterial, parasitic, fungal, viral infections and from the growth of tumor cells. Many of these cell types have specialized functions. Among which, T cells plays a central role in adaptive immunity. T cells are capable of killing viral-infected cell directly (cytotoxic T cells) or help B cells to produce antibodies(helper T cells). Cytokines produced by T cells are also the activation signals for many other immune cells. Patients with T cell deficiency are often more likely to get infections and tumors that do not affect people with working immune systems.
T cells originate from HSC in the bone marrow but develop and mature in thymus. The late development of thymocytes is dictated by T cell receptor signaling and is delicately controlled in molecular level. Although many of the molecular components that regulate TCR signaling and thymocyte selection have been well characterized, the precise interactions between these molecules and the assembly of signaling complexes remains elusive. Now scientists from Institute of Immunology, Zhejiang University School of Medicine described a previously uncharacterized T cell-expressed protein, Tespa1, which plays a critical role during the late development of thymocytes. This work is posted online by Nature Immunology on May 6th.
Tespa1 is identified by Dr. Linrong Lu and his colleagues from data-mining for genes highly expressed in thymocytes. They later developed Tespa1 deficient mice. Dr. Di Wang and Mingzhu Zheng analyzed the Tespa1-/- mice and found that Tespa1-/- mice harbored decreased numbers of mature thymic CD4+ and CD8+ T cells, reflecting impaired thymocyte development. Further work revealed that Tespa1 associated with TCR signaling components PLC-g1 and Grb2 and Tespa1deficiencyresulted in attenuated TCR signaling. These findings demonstrate that Tespa1 is a component of TCR signalosome and is essential for T cell selection and maturation through regulation of the TCR signaling during T cell development.
“Our studies suggest that Tespa1 may be a previously-unsuspected missing link in the TCR-proximal signaling machinery.” Lu remarks. “Further characterization of the basic biological functions of this protein may provide additional insight into our understanding of current models of TCR signaling and thymocyte selection.”
In addition to lead author, Dr. Di Wang and Mingzhu Zheng of Zhejiang University School of Medicine, Coauthors include Lei Lei, Jian Ji, Yunliang Yao, Yuanjun Qiu, Lie Ma, Jun Lou, Chuan Ouyang, Xue Zhang, Yuewei He, Jun Chi, Lie Wang, Ying Kuang, Jianli Wangand Xuetao Cao.
This work was supported by grants from the National NaturalScience Foundation of China, Zhejiang Provincial Natural Science Foundation of China and National Basic Research Program of China.
