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

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40 30 20 10 20 number of peptide-MHC complexes 40 60 80 calcium uptake