Presentation on theme: "Fc Receptors Oct. 28, 2009 Extra reading on web Daniel Conrad 423 MSB, 828-2311 I. CD23."— Presentation transcript:
Fc Receptors Oct. 28, 2009 Extra reading on web Daniel Conrad 423 MSB, 828-2311 I. CD23
CD23 – Member of the C-type animal lectin family
Trimeric structure means Avidity is important in Binding.
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
Current Model for the Fc RI Shows interaction of -chain with IgE
Fc RI 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 Fc RI, RIIIA
Depending on where it is expressed – can exist as or as
Cyrstal structure of complex has revealed site of interaction.
Fc RI is part of a family of Multichain immune recognition Receptors (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 produces IP3 – this releases intracellular Ca and opens CRAC (Ca release activated channels) (Cell 94:5-8, 1998 – reference for above figure if needed)
PH is Pleckstrin Homology domain – binds PI 3,4,5 P3
Fc RI Mechanism ITAMs become phosphorylated (lyn) and bind syk, which then becomes activated Syk and Fyn activate– PI3 kinase – produces PtdIns-3,4,5 P 3 –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
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