T cell Activation and Signaling Flashcards
What are the 3 steps needed for T helper activation?
- TCR + Ag bound to MHC
- Costimulation and survival signals
- Cytokine signaling
What signal must occur for any T helper activation to occur?
TCR + Ag bound to MHC binding
What cytokines cause proliferation? What do the other cytokines signal?
IL-2 signals proliferation and the other cytokines signal differentiation
What do exopeptidases do?
Break down peptides that will not become bound to MHC into amino acids
What cells bind MHC I + peptide?
CD8+ (cytotoxic) T cells
What cells bind MHC II + peptide?
CD4+ (helper) T cells
Describe the affinity of TCRs for MHC?
TCRs have a low affinity for MHC.
How do TCR-Ag-MHC complexes stay together long enough to generate a signal?
Accessory/adhesion molecules such as:
- CD4 (surface adhesion molecule) with MHC II (holds onto the side of MHC structure) or CD8 with MHC I
- CD28 on T cell with CD80/CD86 on APC (both structures hold onto each other)
- LFA from T cell bound to ITAM of APC (very strong interaction)
What are CD4 and CD8?
Coreceptors that bind MHC and are required for the TCR signal
ITAM
Immunoreceptor Tyrosine-based Activation Motif
Allows kinases to recognize these areas so that they can be phosphorylated
What types of proteins are involved in TCR and BCR signaling?
- Tyrosine as well as serine/ threonine kinases
- protein phosphatases
- lipid kinases and lipases
- G proteins
- Transcription factors
Why is tyrosine phosphorylation important?
- it regulates a proteins enzymatic activity
- it regulates interactions between proteins
- it regulates a proteins subcellular localization
What does the SH2 domain of the Src family tyrosine kinases (SFKs) do?
Binds the tyrosine phosphorylates sequences
How does tyrosine phosphorylation modify the protein function?
It can change the shape of the subunits to prevent binding/ transcription of genes
Ex: The Src (kinase) gene is closed/ inactive when the NR region is phosphorylated and the phosphate binds to the SH2 region of the gene. The gene becomes primed when CD45 removes the phosphate and opens up the gene. The gene becomes activated when the kinase portion becomes phosphorylated. Then when the gene needs to be turned off the kinase becomes dephosphorylated by CD45 and Shp1 and then SH2 becomes phosphorylated via Csk (kinase)
What are the signaling steps for CD4+ T cell activation?
- TCR binds to MHC + AG
- CD4 binds to MHC
- CD4 brings along a kinase, Lck which is inactive due to phosphorylation on the regulatory domains
- CD45 dephosphorylates Lck and then it auto phosphorylates itself at another tyrosine site
- The Lck phosphorylates ITAMs of CD3 (making P-ITAMs)
- ZAP70 is attracted to P-ITAMs and is phosphorylated by Lck (making P-ZAP70)
- P-ZAP70 phosphorylates LAT (linker protein of activated T cells)
- PLCgamma1 is attracted to the P-LAT and becomes phosphorylated bt P-ZAP70
- P-PLCgamma1 metabolizes PIP2 into IP3 and DAG
- Ca2+ and DAG facilitate activation of transcription factors that are needed for T cell function
