This study suggests that having so many ITAMs gives T cells greater flexibility in responding to threats. The research was published online February 3. Earlier work from Vignali's laboratory showed that mice whose T cells had as few as two working ITAMs could produce cytokines, molecules that combat infection by fueling inflammation. Those T cells, however, could not proliferate.
This study helps to explain why. The new study showed that without a full complement of ITAMs, T cell receptors did not assemble the machinery needed to launch proliferation. That meant proteins named Notch1 and Vav1 did not interact and connect to the T cell receptor. The study showed that these interactions were required to turn on production of another protein, c-Myc, which in turn drives proliferation.
Previous research from the laboratory of Douglas Green, Ph.D., chair of the St. Jude Department of Immunology, showed c-Myc plays a key role in preparing T cells for rapid proliferation. Until this study, however, the steps involved in inducing c-Myc production were unknown.
"Our study shows that Notch1 activation is required for maximal T cell proliferation," Vignali said. The study identified the importance of Notch1 and its association with the T cell receptor, via Vav1, in T cell proliferation. The researchers also showed that fewer functional T cell receptor ITAMs meant less Notch1 was activated.
The perceived strength of the T cell receptor signaling response also affected c-Myc expression in T cells but not cytokine secretion. T cells gauge their response in part by how strongly an antigen binds to the T cell receptor. Antigens are the pieces of the virus or other invader that alert T cells to a problem. A strong bond triggers higher levels of c-Myc and more proliferatio
|Contact: Summer Freeman|
St. Jude Children's Research Hospital