24–9 Before exposure to a foreign antigen, T cells with receptors specific for the antigen are a tiny fraction of the T cells—on the order of 1 in 105 or 1 in 106 T cells. After exposure to the antigen, only a small number of dendritic cells typically display the antigen on their surface. How long does it take for such antigen-presenting dendritic cells to interact with the antigen-specific T cells, which is the key first step in T cell activation and clonal expansion? The dynamics of the search process were examined by labeling dendritic cells red and T cells green, so that contacts in an for the thymus to actively promote the survival, matura tion, and emigration of developing T cells that bind weakly to self peptides bound to self MHC molecules. Would it not be safer to get rid of these T cells, along with those that bind strongly to such self-peptide–MHC complexes, as this would seem a more secure way to avoid autoimmune reactions?
24–11 CD4 proteins on helper and regulatory T cells serve as co-receptors that bind to invariant parts of class II MHC proteins. CD4 is thought to increase the adhesion between T cells and antigen-presenting cells (APCs) that are initially connected only weakly by the T cell receptor bound to its specific peptide–MHC complex. To test this possibility, you label cell-surface MHC molecules with a fluorescently labeled peptide so that you can detect individual peptide–MHC complexes at the interface between the APCs and the T cells in a culture dish. To detect T cell responses—the sign of a productive contact—you load them with a Ca2+ indicator dye, as cytosolic Ca2+ increases when lymphocytes are active. You now count the peptide– MHC complexes at a large number of interfaces (immunological synapses) and measure the resulting uptake of Ca2+ in the adherent T cells (Figure Q24–4, red circles). When you repeat the experiment in the presence of blocking antibodies against CD4, you get a different result (blue circles). Do these results support or refute the notion that CD4 augments T cell receptor binding? Explain your answer.
Figure Q24–4 role of cD4 in the T cell response (problem 24–11). The uptake of ca2+ in cells with different numbers of fluorescently complexes at the interface between the T cells and the ton fluorescence microscopy (Figure Q24–3A). The fre quency of contacts between dendritic cells and T cells antigen-presenting cells.
The results in the absence from such experiments is given in Figure 24–3B. Assuming are shown by the red curve; that 100 dendritic cells present the specific antigen, how long would it take them to scan 105 T cells? How long for results in the presence of 0 20406080 cD4 antibodies are shown 106 T cells? number of peptide–MHC complexes by the blue curve.
Murphy K (2011) Janeway’s Immunobiology, 8th ed. new York: Garland Science.
Abbas AK, Lichtman AH & Pillai S (2014) cellular and Molecular Immunology, 8th ed. Philadelphia: WB Saunders.
Parham P (2015) The Immune System, 4th ed. new York: Garland Science.
The Innate Immune System
Beutler B & Rietschel eT (2003) Innate immune sensing and its roots: the story of endotoxin. Nat. Rev. Immunol. 3, 169–176.
Davis BK, Wen H & Ting JP (2011) The inflammasome nLRs in immunity, inflammation, and associated diseases. Annu. Rev. Immunol. 29, 707–735.