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Fc Receptors Oct. 28, 2009 Extra reading on web Daniel Conrad 423 MSB, 828-2311 I. CD23.

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Presentation on theme: "Fc Receptors Oct. 28, 2009 Extra reading on web Daniel Conrad 423 MSB, 828-2311 I. CD23."— Presentation transcript:

1 Fc Receptors Oct. 28, 2009 Extra reading on web Daniel Conrad 423 MSB, I. CD23

2 CD23 – Member of the C-type animal lectin family

3 Trimeric structure means Avidity is important in Binding.

4 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

5 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

6 Fc  RI

7 Initial model for the Fc  RI 1982

8 Current Model for the Fc  RI Shows interaction of  -chain with IgE

9 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

10 Depending on where it is expressed – can exist as  or as 

11 Cyrstal structure of complex has revealed site of interaction.

12 Fc  RI is part of a family of Multichain immune recognition Receptors (MIRRs) that use an ITAM activation scenario

13 ITAM Motif

14 ITAM (aggregation)

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16 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)

17 PH is Pleckstrin Homology domain – binds PI 3,4,5 P3

18 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

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21 Summary of FcR structure showing ITAMs or ITIMs in cytoplasm

22 Cartoon showing glycerol-phosphotidyl inositol (GPI) linked protein PLD and PLC are enzymes that cleave at positions indicated

23 KAR is NK activating receptor

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30 Examples of proteins that have an ITIM in cytoplasm

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32 “ITIMs control ITAMs”

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35 Mechanism of SHIP – cleaves 5’ phosphate from PI3,4,5-P3 – then IP3 cannot be made – blocking calcium release.

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37 Fc receptor cluster in mouse and human

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39 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

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41 FcγRIV Expressed in mouse – binds IgG2a/2b best Expressed on macrophages and dendritic cells Opsonic Fc receptor – especially for these subclasses of IgG

42 IgA Transport

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