![]() ![]() ![]() T cells represent major components of the cellular arm of the adaptive immune response. The lack of correlation between CD45 segregation and early markers of T cell activation suggests that segregation of CD45 from engaged TCRs is not mandatory for initial triggering of TCR signaling by elongated high-affinity ligands. In addition, at early times, triggering cells with both high and low affinity elongated anti-CD3 scFv resulted in similar degrees of CD3 co-localization with CD45, but only the high-affinity scFv induced T cell activation. Both short and elongated high-affinity anti-CD3 scFv effectively induced similar calcium mobilization, Zap70 phosphorylation, and cytokine secretion in Jurkat T cells but CD45 segregated from activated TCR microclusters significantly less for elongated versus short anti-CD3 ligands. We examined CD45 segregation from TCRs engaged to anti-CD3 scFv with high or low affinity and with defined molecular lengths on glass-supported lipid bilayers using total internal reflection microscopy. However, whether CD45 segregation is important to initiate triggering is still uncertain. It has been proposed that segregation of the large membrane tyrosine phosphatase CD45 from engaged TCRs initiates signaling by favoring phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic domains of CD3 molecules. How T cell receptors (TCRs) are triggered to start signaling is still not fully understood. 5Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.4Brain Research Center, National Yang-Ming University, Taipei, Taiwan.3Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.2Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University, Academia Sinica, Taipei, Taiwan.1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. ![]()
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