Halflife of Antibodies

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Different antibody isotypes have very different half-lives in circulation. IgE has a very short half-life of about 2 days in the circulation (although cell-bound IgE associated with the high-affinity IgE receptor on mast cells has a very long half-life; see Chapter 19). Circulating IgA has a half-life of about 3 days, and circulating IgM has a halflife of about 4 days. In contrast, circulating IgG molecules have a half-life of about 21 to 28 days.

The long half-life of IgG is attributed to its ability to bind to a specific Fc receptor called the neonatal Fc receptor (FcRn), which is also involved in the transport of IgG from the maternal circulation across the placental barrier as well as the transfer of maternal IgG across the intestine in neonates. FcRn structurally resembles MHC class I molecules but lacks a peptide-binding groove, and in specific cell types, such as the placenta and the neonatal intestine, it transports IgG molecules across cells without targeting them to lysosomes. In adult vertebrates, FcRn is found on the surface of endothelial cells (and other cell types) and binds to micropinocytosed IgG in acidic endosomes. FcRn does not target bound IgG to lysosomes but sequesters the IgG for a while and then returns it to the circulation, when it recycles to the cell surface and releases the IgG at neutral pH (Fig. 5-11). This intracellular sequestration of IgG for significant periods prevents it from being targeted for degradation

FIGURE 5-11 FcRn contributes to the long half-life of IgG molecules. Micropinocytosed IgG molecules in endothelial cells bind the FcRn, an IgG-binding receptor in the acidic environment of endosomes. In endothelial cells, FcRn sequesters IgG molecules and releases them when vesicles fuse with the cell surface, exposing FcRn-IgG complexes to neutral pH.

Serum protein

IgG released from FcRn by Nf extracellular pH

Serum protein

IgG released from FcRn by Nf extracellular pH

FIGURE 5-11 FcRn contributes to the long half-life of IgG molecules. Micropinocytosed IgG molecules in endothelial cells bind the FcRn, an IgG-binding receptor in the acidic environment of endosomes. In endothelial cells, FcRn sequesters IgG molecules and releases them when vesicles fuse with the cell surface, exposing FcRn-IgG complexes to neutral pH.

Recycling Endosome

complexes sorted to recycling endosome

IgG binds to FcRn in endosome

FcRn

IgG binds to FcRn in endosome

FcRn

Recycling Endosome

Recycling endosome complexes sorted to recycling endosome

Lysosome

Endosome pH ~2.0

Lysosome

Other proteins1 degraded in lysosomes as rapidly as most other serum proteins, including other antibody isotypes, and as a result, IgG has a relatively long half-life. This long half-life of IgG has been used to provide a therapeutic advantage for certain infused proteins by producing fusion proteins containing the biologically active part of the protein and the Fc portion of IgG. One therapeutically useful fusion protein is TNFR-Ig, which consists of the extracellular domain of the type II TNF receptor fused to an IgG Fc domain; it is used to treat certain autoimmune disorders, such as rheumatoid arthritis and psoriasis, in which it blocks the inflammatory actions of TNF. Another therapeutically useful fusion protein is CTLA4-Ig, which contains the extracellular domain of the CTLA-4 inhibitory receptor fused to the Fc portion of human IgG; it has also been used in the treatment of rheumatoid arthritis and may serve more broadly as an immunosuppressive therapeutic (see Fig. 9-7, Chapter 9).

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Responses

  • fabiana
    What is half life in immunology?
    2 years ago
  • elena
    What is halflife af antibodies in lungs?
    2 years ago
  • james
    What is the half life of IgG in humans?
    2 years ago
  • Tekle
    What is the halflife of an IgG antibody?
    2 years ago
  • FATIMA BAGGINS
    What do antibodies have such long half lives?
    2 years ago
  • merigo
    WHAT IS THE HALF LIFE OF AN IGG ANTIBODY?
    1 year ago
  • ada
    What is average half life igg human?
    1 year ago
  • John McRee
    How to measure antibody half life?
    7 months ago
  • mark
    Are there long life antibodies?
    6 months ago
  • Ari
    How to calculate antibody half life?
    5 months ago
  • welde
    What is the typical hal life of a mouse antibody?
    4 months ago
  • BEATRICE
    Which antibody has a half life of 23 days?
    4 months ago
  • Letteria Calabresi
    Why igg has longer half life?
    3 months ago
  • gabriel
    What is long half life of antibody in cuynomolgus?
    2 months ago
  • orla
    What is the half life of IgG1?
    1 month ago
  • Jaime
    What is the half life of antibodies?
    29 days ago

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