Title: Ig Isotypes and Fc Receptors
1Ig Isotypes and Fc Receptors
- Penny Morel
- April 2, 2007
- morel_at_pitt.edu
2Ig isotypes structural features
489, 2004
3Figure 9-19
4Role 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)
5Fundamental Immunology Textbook.
6489, 2004
7489, 2004
8Figure 9-31
9Figure 9-32 part 1 of 2
10Figure 9-32 part 2 of 2
11Figure 9-34
12Figure 9-35
13Fc receptors are multimolecular complexes
14FceR1 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
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16Signaling cascade - ITAM
17New 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
18FcR isotype binding specificity
Fc?RIIb Fc?RIII Fc?RIV
19IgG2a is most effective in ADCC
Science 3101510, 2005
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21Inhibition 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
22Other inhibitory Receptors Not a complete list!
23Inhibits IgE mediated degranulation of mast cells
2773, 2002
24FcgRIIB on B cells
Functions to prevent naïve B cell activation when
IgG is present and to control B cell activation.
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26Immunity 2419, 2006
27FcgRIIB -/-
- Spontaneously develop autoantibodies
- More susceptible to autoimmune disease models -
collagen induced arthritis - Enhanced antibody response to antigen
28FcgRIIB -/- mice develop anti-DNA antibodies
29Role of FcgR in collagen induced arthritis
FceR1 g -/- protected FcgRIIB -/- more
susceptible J. Exp. Med. 1911611, 2000
30Activation/inhibition
31Cytokines influence FcR expression
32Antibody 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
33Other Fc Receptors
34FceRII/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
35FcaR1 (CD89)
- Binds IgA1 and IgA2
- Low affinity
- Macs, PMN and eosinophils
- Induces Ag uptake and pathogen killing
- Associates with FceR1 g chain
36Transport 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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