Signaling of Naive T & B Cells Flashcards
Quiz 4
When are transmembrane receptors needed during signaling
Needed when signals can’t cross the membrane on their own
Describe the function of receptor tyrosine kinase (RTK)
-upon binding, activates a kinase (separate protein)
-upon binding of ligand, it will dimerize and then autophosphorylates
What are two examples of proteins that propagate signal
-kinases
-scaffold proteins
What domain in RTK’s play a key role in propagating signal
SH2 (how it phosphorylates tyrosine)
What does a scaffold protein do
-Activation of a protein kinase results in phosphorylation of a scaffold
-phosphorylated scaffold requires signaling proteins and brings them closer together
-also brings them to the membrane
What changes do most signaling pathways end
-Changes to transcription factors
-Rewires the cells trancriptome/proteome
-can range from simple (few genes) to complex
What are two ways signaling pathways are turned off
-phosphatases (dephosphorylate)
-ubiquitin (degradation of receptor)
What are three components of the T cell Receptor (TCR)
-alpha beta receptor (insufficient for signaling)
-CD3 complex
-gamma domain (completely intracellular)
-Positive, transmembrane pieces
Where are ITAM (Immunoreceptor Tyrosine-based Activation Motifs) found
-Found in signaling proteins for
-Tcells
-B cells
-NK
-Phagocytes
-Ab sensing (Fc receptor)
Explain the activation of the TCR
-Requires co-receptor (CD4: MHC II Th and CD8: MHC I cytotoxic)
-Binding leads to ITAM phosphorylation
-Recruite downstream proteins
What is Lck
-SCR-family kinase
-boudn to CD4 or CD8
-Phosphorylates ITAMs
-Kept inhibited until activated
What is PIP3
membrane bound and forms both a soluble and membrane-bound signals after PLC cleavage
What are the 2 outcomes of PLC cleavage of PIP3
-Ras signaling
-Induces CA2+ release
What is an immune synapse
-TCR-MHCII complex
-Integrins
What are BCR (B-cell Receptor)
-antibodies are screted (need to become receptors)
-Antibody is generated with a transmembrane domain
-Interacts with Igalpha and Igbeta (help in trafficking and contains ITAMS
Explain how BCR binding activates SRC-family kinases
-free antigen binds with multivalency (multiple epitopes on antigen: CROSSLINKING)
-leads to phosphorylation of ITAMs on B-cell receptor tails by SRC-family kinase
-Sky binds to double phosphorylated ITAMs and is activaed on binding
What is an alternative method of B-Cell activation
-using co-receptor
-CD21 (CR2) binds a C3 freagment
-Antigen + complement= activation
What are two receptors that regulate antigen receptor signaling
-APCs can express co-stimulatory molecules (induced by PRR/ cytokine signaling)
-Robust T cell receptor activation requires (antigen presentation on MHC and co-stimulatory signal)
What is the role of CD28
-on naive T cell, recognizes B7.1 or B7.2
-B7 is expressed only on ‘activated’ APC
-Recognition by CD28 leads to high PIP3 (PIP3 is also induced by TCR)
-The two activated lead to max PIP3
What are two things required for T-cell activation
-TCR
-CD28
What is CD40
-TNF-superfamily receptor
-very different from RTK’s
-When not activated (TRAF molecules UB-ate NIK and NIK degraded)
What happens upon activation of CD40
-TRAF is degraded
-NIK phosphorylates the IKK
-IKK activates NFkB
What happens when NFkB is activated by CD40
-Non-canonical NFkB activation pathway
Why do activated T cells start expressing inhibitory receptors
Prevents over-activation (can even inhibit other T cells)