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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

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Fc receptors oct 28 2009 extra reading on web

Fc ReceptorsOct. 28, 2009 Extra reading on web

Daniel Conrad

423 MSB, 828-2311

I. CD23



Trimeric structure means

Avidity is important in

Binding.


Cd23 summary
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
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


Fc e ri

FceRI



Current Model for the FceRI

Shows interaction of a-chain

with IgE


Fc e ri composition
FceRI composition

  • Three proteins required for expression in rodent – though a,g2 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 FcgRI, RIIIA




Fc interaction.eRI is part of a family of Multichain immune recognition

Receptors (MIRRs) that use an ITAM activation scenario


ITAM Motif interaction.


(aggregation) interaction.

ITAM


Receptor activates PTK either directly or indirectly – recruits syk family – activates

PI3K which phos. PI3,4,5P3 – this recruits PLCg 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)



Fc e ri mechanism
Fc recruits syk family – activates eRI 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 PLCg 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) recruits syk family – activates

linked protein

PLD and PLC are enzymes that cleave at positions

indicated


KAR is NK activating receptor recruits syk family – activates


Examples of proteins that recruits syk family – activates

have an ITIM in cytoplasm


“ITIMs control ITAMs” recruits syk family – activates


Mechanism of SHIP – cleaves 5’ phosphate from PI3,4,5-P3 – then

IP3 cannot be made – blocking calcium release.



Evidence that another Fc Receptor was present – then

  • 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


Fc riv
Fc – thenγRIV

  • Expressed in mouse – binds IgG2a/2b best

  • Expressed on macrophages and dendritic cells

  • Opsonic Fc receptor – especially for these subclasses of IgG


IgA Transport – then


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