They first exposed APCs to a peptide that is known to be a strong antigen for the T cell clone under study. This approach is novel because it quantifies the initial input stimulus during the natural interaction between APC and T cell and then measures the final output of signal processing. These two cytokines are important regulators of the adaptive immune response and their secretion can be considered as indicator for CD4 + T cell effector function. They developed techniques to count the number of pMHC present in the immunological synapse while simultaneously quantify the secretion of IL-2 and TNF-α by T cells. 4 imaged CD4 + T cells in contact with APCs using 3D microscopy. For CD4 + T cells, antigen engagement turns the cells into effectors cells that help other immune cells via cytokines or cell-cell contacts and thus elicit a concerted immune response against pathogens. TCR discriminates foreign from self antigens and initiates signaling pathways to activate T cells. The adaptive immune response against invading pathogens starts from the specific engagement of the T-cell receptor (TCR) on the T cell surface with the antigenic peptides displayed by MHC molecules (peptide-MHC complex, pMHC) on the surface of antigen-presenting cells (APCs). 4, which studied T cell activation at single-molecule and single-cell level and demonstrated that T cells undergo digital immune response upon antigen stimulation. Motivated by this exciting idea, we would like to highlight a paper by Huang et al. Emerging evidence reveals that remarkable traits of T cell responses might be due to digital signaling. While digital signaling is known to convert multiple inputs into all-or-nothing action potentials in neurons 3, the function that it might have in some, if not all, non-excitable cell types remains to be elucidated. Thus, the population shows a gradually increasing activation while single cells show either “on” or “off”. While the level of translocated transcription factors in activated cells remained constant, increasing stimuli led to a higher percentage of activated cells. In cells stimulated with TNF-α (for NF-κB) or Leukotriene C4 (for NFAT1), these transcription factors showed either high levels of nuclear translocation and subsequent gene expression or none at all. This was recently shown to be the case for nuclear factor κB (NF-κB) 1 and nuclear factor of activated T cells 1 (NFAT1) 2. When measured at the single-cell level, various signaling pathways show digital responses, i.e., they respond to stimuli by activating key molecules in an all-or-nothing manner. There is increasing evidence that population-wide measurements do not necessarily reflect single-cell behavior. Measured at a population level, these responses (e.g., effector molecule production) typically increase with ligand concentrations. The contact between receptor and ligand is the starting point of signaling pathways that ultimately result in a cellular response.
Mammalian cells sense extracellular stimuli through cell surface receptors.
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