Question 2: (5.5 points) Co-stimulatory and inhibitory receptors modulate antige

Question

Question 2: (5.5 points) Co-stimulatory and inhibitory receptors modulate antigen receptor signaling in T and B IymphocVtes. A new receptor is discovered, expressed on the surface of T cells, and called 'X'. An antibody to X is generated, and used in T cell stimulation experiments. In these experiments, antibodies to the TCR complex (anti- CD3) and to CD28 (anti-CD28) are known to stimulate signaling through those receptors, as does the antibody to X. The data from an experiment measuring IL-2 secretion by the T cells stimulated with different combinations of antibodies are shown in the figure below. IL-2 (pg/m 6000 4000 2000 No stim Anti-CD3 Ant-C028 Anti-C3 Ant-X Anti-CD3 Anti-CO3 anti-CO2B anti-X anti-CO28 anti-X a) Does stimulation of receptor X alone induce IL-2 production by T cells? Does it enhance or inhibit TCR signaling? Indicate the evidence supporting your answers. (1.5 points) b) If you examined the amino acid sequence of the receptor X cytoplasmic tail, what motif would you expect to find? (0.5 point) Biochemical studies show that when receptor X is stimulated, a tyrosine residue in the cytoplasmic tail becomes phosphorylated c) From these data, what are the two most likely signaling proteins that might be recruited to receptor X when it is stimulated? Does the T cell stimulation data shown in the graph rule in or out either of your candidate proteins? Why or why not? (1.5 points) d). Read the sections on blots in the textbook (pages 762-764). Use this to information to describe an experiment you could do to determine which enzyme is recruited to receptor X when it is stimulated. (2 points) ?? and Western

Explanation / Answer

a) Receptor X inhibits TCR signalling. The graph indicates that

b) The cytoplasmic tail of receptor X contain have multiple copies of the Immuno-receptor Tyrosine Activation Motif (ITAM), which contain tyrosines that become phosphorylated in the signal transduction through the receptor. Phosphorylation of ITAM-tyrosine residues allows docking of adapter molecules, thus facillitating initiation of the signalling cascade.

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