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

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. IL-2 (pg/ml 6000- 4000 2000 No stim Anti-CD3 Ani-CD28 Ani-CO3 Anti-X Anti-CD3 Anti-CD3 anti-C028 ani-X anti-CD28 ant-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. (4 points) b) If you examined the amino acid sequence of the receptor X cytoplasmic tail, what motif would you expect to find? (2 points) c) Biochemical studies show that when receptor X is stimulated, a tyrosine residue in the cytoplasmic tail becomes phosphorylated. 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 shewn in the graph rule in or out either of your candidate proteins? Why or why not? (4 points)

Explanation / Answer

a)      As shown in the figure, receptor X activation gives a little production if IL-2 (almost negligible). When CD3 and CD-28 are activated in combination, huge IL-2 production was observed (it mean high level of activation of T-cell). But when CD3 and CD-28 are activated along with receptor X, IL-2 production decreased, this shows that Receptor X activation inhibits T-cell receptor signalling.

b)      The cytoplasmic region of X-receptor on T-cells contain conserved motif called as ITAM (immunoreceptor tyrosine-based activation motif). This motif is very important for TCR (T-cell receptor) signalling as cytoplasmic tails of TCR are very short. Phosphorylation of ITAM motifs leads to further signalling inside the cell by activating various other enzymes or molecules.

c)      Receptor X activation cay triggers phosphorylation of cytoplasmic tail containing tyrosine residues (ITAM motifs). The signalling proteins may undergo activation after this, are Lck or FYN or CD45 or Zap70 (these are various proteins activated in T-cell activation).

Related Questions

Navigate

• Browse (All)
• Browse C
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.