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Triggering the Cascade: Foreign Antigen Activates T-Cell Receptor


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Making Waves: Cytoplasmic Signals Cause the Release of Calcium

Have students watch the animation in pairs. They should focus first on the four major themes and then view actions and descriptions of specific molecules. Provide students with some directed questions. Students can also prepare presentations related to the animation. Topics might include signal transduction cascades, molecular switches, assembly of molecules at docking sites, or targets for drug design.

Activating Important Molecules Near the Membrane: ITAM, ZAP-70, and Other Kinases

4. What do these general regulatory principles tell us about molecular switches? For example, there are many levels of control, pathways intersect, and many molecules need to be activated (that is, switched "on") in order for the molecule to do its job.

Turning on Genes: Initiation of IL-2 Gene Transcription

The Message Moves into the Cell: Membrane Complexes Transmit the Signal into the Cytoplasm

View the animation to see how one type of immune cell—the helper T cell—interprets a message presented at the surface of the cell membrane. The message is an antigen, a protein fragment taken from an invading microbe. A series of events unfolds that results in the production of many clones of the helper T cell. These identical T cells can serve as a brigade forming an essential communication network to activate B cells, which make antibodies that will specifically attack the activating antigen.

The animation illustrates several fundamental biological principles and processes common to many cellular functions. It may be helpful to view the animation several times, first to gain a general impression of the signal transduction process and then to focus on particular molecular details.

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An Army of Clones: IL-2 Binding to Receptor Causes T Cell Proliferation

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Roitt, I., Brostoff, J., and Male, D. . 4th ed. London: Mosby, 1996; pp. 4.1–6.12.
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  • Pathogenic Infection Mechanism (Infectious Diseases)

    Photosynthesis (Light): The Movie. For a text version of this narrative, click here.

  • Intracellular Infection by (Infectious Diseases)

    Virtual Cell Animations - Photosynthesis

  • References Used in Developing the Animation

    photosynthesis dark phase

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Activates the docking- site molecule

2. Discuss dephosphorylation by phosphatases. Does dephosphorylation always inactivate a molecule? (No.) Discuss how in the animation, NF-AT (nuclear factor of activated T cells) cannot pass through the nuclear membrane in its phosphorylated state. However, when dephosphorylated, it passes through the membrane and can initiate gene transcription of IL-2.

Activates the docking-site molecule

2. Compare the signal transduction cascade in the helper T cell with that occurring in other cells in other biological processes. Discuss messenger molecules that are used by many cell types, such as IP3 and Ca++. Consider showing other animations that describe these processes in more detail.

Blocking Molecular Transduction Cascades with Drugs

1. Discuss the process that occurs in signal transduction cascades. In the animation illustrating T-cell proliferation, signal transduction begins when a foreign antigen carried by the antigen-presenting cell (APC) is recognized by the T-cell receptor. Several molecules located in or near the cell membrane mediate the transmission of signals, resulting in the production of inositol triphosphate (IP3), which travels into the cell's cytoplasm. IP3 initiates the release of calcium, which, through several intermediate steps, allows a transcription factor to enter the nucleus. Within the nucleus, this transcription factor and other essential factors trigger the expression of the gene interleukin-2 (IL-2). IL-2 protein is produced and released extracellularly, where IL-2 binds to receptors on the T cell. This receptor/IL-2 protein complex signals the T cell to proliferate.

Collaborative Learning and Communication

1. Describe how the animation demonstrates that molecules have multiple functions. For example, ZAP-70 (zeta-associated protein-70) both docks at a site—ITAM (immunoreceptor tyrosine-based activation motif)—and prepares another docking site—LAT (linker for activation of T cells).

Scientific Direction: Andrew Chan, Ph.D.

Zhang, W., Sloan-Lancaster, J., Kitchen, J., Trible, R.P., and Samelson, L.E. 1992. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. 92 (1): 83–92.

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