10. Lymphocyte receptor signalling Flashcards
a primary response to an antigen causes:
clonal expansion of antigen-reactive T or B cells
what is the function of signal transduction pathways
control transcriptional and metabolic pathways
determine lymphocyte function
membrane receptors have 3 domains:
- extracellular domain: binds ligand
- transmembrane domain: span the PM
- cytoplasmic domain: participate in signal transduction
ligands for TCR and BCR
TRC: peptide + MHC
BCR: antigen
what is the immunological synapse
the space between the T cell and APC where receptor-ligand binding occurs in order for signal transduction to happen
T cells are activated through 2 signals…
signal 1: MHC + peptide on APC binds TCR
signal 2: B7 on APC binds CD28 on naive T cell (costimulatory signal)
what is the costimulatory signal in T cell activation
B7 binds CD28
B7 is only expressed if infection is present
what makes up the immunological synapse
TCR and MHC:peptide complex
co-stimulatory molecules
co-receptor and MHC:peptide complex
cell-adhesion molecules
what is CD3
the cytoplasmic domain of the TCR that relays the signal from the synapse so that signal transduction can start
what are ITAMs
immunoreceptor tyrosine-based activation motifs
cytoplasmic aa sequences containing tyrosine that are targets of phosphorylation
docking sites for other proteins
mediate interactions with cytoplasmic protein-tyrosine kinases
what are the protein-tyrosine kinases in TCR signal transduction
Lck and ZAP-70
what is the key event in TCR signal transduction
the phosphorylation of ZAP-70 by Lck
induces 3 signal transduction pathways
1st signal transduction pathway of TCRs: NFAT actiavtion
- phosphorylation and activation of PLCy
- cleavage of PIP into IP3 and DAG
- IP3 signals calcium stores to open
- Ca2+ diffuses through the cell
- calcineurin is activated and dephosphorylates NFAT
- NFAT acts as a TF and activates genes for T-cell expansion and differentiation
2nd signal transduction pathway of TCRs: NFkB activation
- phosphorylation and activation of PLCy
- cleavage of PIP into IP3 and DAG
- DAG activates PKC
- PKC activates the NFkB through destruction of associated IkB protein
- NFkB acts as a TF and activates genes for T-cell expansion and differentiation
3rd signal transduction pathway of TCRs: AP-1 activation
- phosphorylation and activation of PLCy
- cleavage of PIP into IP3 and DAG
- DAG associates with RAS
- RAS triggers MAP kinase cascade to activate Fos
- Fos interacts with Jun to produce AP-1
- AP-1 acts as a TF and activates genes for T-cell expansion and differentiation