CD23 Summary
• Only Fc receptor that with no relationship to Ig superfamily
• Two isoforms exist – differ only in first six amino acids (in cytoplasm)
• Cleaved form loses trimeric structure – only interacts with IgE with low affinity
• Other ligands as well – CD21, CD11/CD18
CD23 Function
• Isotype control – IgE synthesis
• Antigen presentation – IgE complexes are internalized and degraded – peptides are then associated with class II MHC
• B cell growth and differentiation – in association with IL-1
FcRI composition
• Three proteins required for expression in rodent – though works in human
• alpha-chain binds IgE• Beta – amplifies signal – binds src related
kinase (lyn).• Gamma – ITAMS are phosphorylated and
interact with syk – this same gamma chain also is associated with FcRI, RIIIA
FcRI is part of a family of Multichain immune recognitionReceptors (MIRRs) that use an ITAM activation scenario
Receptor activates PTK either directly or indirectly – recruits syk family – activates PI3K which phos. PI3,4,5P3 – this recruits PLC and Tec family – which producesIP3 – this releases intracellular Ca and opens CRAC (Ca release activated channels)(Cell 94:5-8, 1998 – reference for above figure if needed)
FcRI Mechanism
• ITAMs become phosphorylated (lyn) and bind syk, which then becomes activated
• Syk and Fyn activate– PI3 kinase – produces PtdIns-3,4,5 P3
– Binds PLC and Tec family member (btk)
– IP3 is produced – causing release of intracellular calcium and influx of calcium (CRAC)
• Syk also activates vav – via SLP -- and eventual gene transcription
Cartoon showing glycerol-phosphotidyl inositol (GPI) linked protein
PLD and PLC are enzymes that cleave at positionsindicated
Mechanism of SHIP – cleaves 5’ phosphate from PI3,4,5-P3 – thenIP3 cannot be made – blocking calcium release.
Evidence that another Fc Receptor was present
• FcRγ KO was more severe than FcγRI or FcγRIII α-chain.
• This was especially true if antibody class was IgG2a/IgG2b and the effector cell was myeloid in nature.
• Fcrl3 – 60% Id with FcγRIII α-chain.
• Charged aa in transmembrane domain
FcγRIV
• Expressed in mouse – binds IgG2a/2b best
• Expressed on macrophages and dendritic cells
• Opsonic Fc receptor – especially for these subclasses of IgG
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