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Co-stimulatory and inhibitory receptors modulate antigen receptor signaling in T

ID: 217677 • Letter: C

Question

Co-stimulatory and inhibitory receptors modulate antigen receptor signaling in T and B lymphocytes. 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.

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 Immunoprecipitation/co-immunoprecipitation and Western 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)

IL-2 (pg/ml) 6000- 4000 2000 No stim Anti-CD3 Anti-CD28 Anti-CD3 Anti-X Anti-CD3 Anti-CD3 anti-CD28 anti-X anti-CD28 anti-X

Explanation / Answer

A. Stimulation of receptor X alone doesn't induce IL-2 production because the level of IL-2 production in the graph is at its basal level. It inhibits TCR signaling because in combination of antibodies anti-CD3 and anti-CD28, level of IL-2 production was very high but after addition of receptor X, the production got decreased , as seen in the last bar.

C. Anti-CD3 and anti-CD28 signaling molecules smight be recrited. Yes, the data ruled in for my candiate proteins because, the expression of IL-2 and effector molecule is clearly understood from the graph.

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