Antigen-triggered T-cell receptor (TCR) phosphorylation is the first signaling event in T cells to elicit adaptive immunity against invading pathogens and tumor cells. Despite its physiological importance, the underlying mechanism of TCR phosphorylation remains elusive. Here, we report a key mechanism regulating the initiation of TCR phosphorylation. The major TCR kinase Lck shows high selectivity on the four CD3 signaling proteins of TCR. CD3e is the only CD3 chain that can efficiently interact with Lck, mainly through the ionic interactions between CD3e basic residue-rich sequence (BRS) and acidic residues in the Unique domain of Lck. We applied a TCR reconstitution system to explicitly study the initiation of TCR phosphorylation. The ionic CD3e−Lck interaction controls the phosphorylation level of the whole TCR upon antigen stimulation. CD3e BRS is sequestered in the membrane, and antigen stimulation can unlock this motif. Dynamic opening of CD3e BRS and its subsequent recruitment of Lck thus can serve as an important switch of the initiation of TCR phosphorylation.T-cell receptor | Lck | initial phosphorylation | substrate selectivity | ionic interaction

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BackgroundGuangxi is the province most seriously affected by rabies virus (RABV) in China. Those most affected by RABV each year are people in rural areas, where dogs are the main cause of human infection with the virus.MethodsIn this study, we established a rabies vaccination demonstration program that included eradication, core, and peripheral areas. This program was implemented for 9 years and comprised three stages: 12 counties in the first stage (2008–2010), 21 counties in the second stage (2011–2013), and then extending to all counties of Guangxi Province in the third stage (2014–2016). The program included a dog vaccination campaign, surveillance of clinically healthy dogs who may be potential RABV carriers, monitoring anti-RABV antibody titers in vaccinated dogs, and compiling and reporting statistics of human rabies cases.ResultsThe target effectiveness was achieved in the eradication, core, and peripheral areas in all three stages. The vaccination demonstration program successfully promoted RABV vaccination of domestic dogs throughout Guangxi Province by drawing upon the experience gained at key points. Compared with a vaccination coverage rate of 39.42–46.85% in Guangxi Province overall during 2003–2007, this rate gradually increased to 48.98–52.67% in 2008–2010, 60.24–69.67% in 2011–2013, and 70.09–71.53% in 2014–2016, thereby meeting World Health Organization requirements. The total cases of human rabies in the province decreased from 602 in 2004 to 41 cases in 2017.ConclusionsThe present pilot vaccination program obviously increased the rabies vaccination and seroconversion rates, and effectively reduced the spread of rabies from dogs to humans as well as the number of human rabies cases, thus successfully controlling rabies in Guangxi.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3301-8) contains supplementary material, which is available to authorized users.