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Ig Isotypes and Fc Receptors

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Provides innate immune system with high degree of ... Defect in IgE-triggered anaphylaxis. No ADCC by NK cells. Signaling cascade - ITAM. New FcR: Fc ... – PowerPoint PPT presentation

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Title: Ig Isotypes and Fc Receptors


1
Ig Isotypes and Fc Receptors
  • Penny Morel
  • April 2, 2007
  • morel_at_pitt.edu

2
Ig isotypes structural features
489, 2004
3
Figure 9-19
4
Role of Fc receptors
  • Link Ig to cells of the innate immune system -
    macrophages, neutrophils, mast cells, NK cells.
  • Provides innate immune system with high degree of
    specificity (Fab portion)
  • Separate Fc receptors for each isotype (6 for
    IgG)

5
Fundamental Immunology Textbook.
6
489, 2004
7
489, 2004
8
Figure 9-31
9
Figure 9-32 part 1 of 2
10
Figure 9-32 part 2 of 2
11
Figure 9-34
12
Figure 9-35
13
Fc receptors are multimolecular complexes
14
FceR1 gamma chain is required for expression of
several FcR
  • Mice lacking FceR1 g chain do not express FceR1,
    FcgRI (CD64), FcgRIII (CD16)
  • Defect in IgE-triggered anaphylaxis
  • No ADCC by NK cells

15
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16
Signaling cascade - ITAM
17
New FcR Fc?RIV
  • Expressed on neutrophils, Monocytes, macrophages,
    DCs
  • Associates with Fc?R1? chain
  • Induced by IFN-?, downregulated by IL-4, IL-10
    and TGF-?
  • Binds IgG2a and IgG2b - not IgG1 or IgG3

18
FcR isotype binding specificity
Fc?RIIb Fc?RIII Fc?RIV
19
IgG2a is most effective in ADCC
Science 3101510, 2005
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Inhibition via FcR
ITIM motif (L/V/I/S)xYxx(L/V) CD32 FcgRIIB1
B, mast cells Inhibition No
uptake FcgRIIB2 Macs, eos, PMN Inhibition
uptake Two isoforms are generated by alternative
splicing
22
Other inhibitory Receptors Not a complete list!
23
Inhibits IgE mediated degranulation of mast cells
2773, 2002
24
FcgRIIB on B cells
Functions to prevent naïve B cell activation when
IgG is present and to control B cell activation.
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Immunity 2419, 2006
27
FcgRIIB -/-
  • Spontaneously develop autoantibodies
  • More susceptible to autoimmune disease models -
    collagen induced arthritis
  • Enhanced antibody response to antigen

28
FcgRIIB -/- mice develop anti-DNA antibodies
29
Role of FcgR in collagen induced arthritis
FceR1 g -/- protected FcgRIIB -/- more
susceptible J. Exp. Med. 1911611, 2000
30
Activation/inhibition
31
Cytokines influence FcR expression
32
Antibody mediated inflammation
  • Type I (immediate hypersensitivity) requires
    FceR1
  • Type 2 (cytotoxic IgG) requires FcgRIII and
    FcgRIV
  • Type 3 (immune complex-induced damage) requires
    FcgRIII
  • FcgRIIB modulates all of these responses

33
Other Fc Receptors
34
FceRII/CD23
  • Low affinity IgE receptor
  • B cells, T cells, monocytes FDC, eos etc
  • May act to enhance Ab response to antigen in
    presence of IgEAg complex
  • Could act by capturing Ab for APC presentation
  • C-type lectin

35
FcaR1 (CD89)
  • Binds IgA1 and IgA2
  • Low affinity
  • Macs, PMN and eosinophils
  • Induces Ag uptake and pathogen killing
  • Associates with FceR1 g chain

36
Transport receptors
  • Poly Ig receptor on epithelial cells for IgA
    transport
  • FcRn MHC class I-like, contains b2m, transports
    IgG to extracellular spaces, and across placenta

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