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Antibody structure and function

What are they?
1. Made of glycoproteins (proteins and carbohydrates) found in serum and tissue fluids.
  1. We can make an antibody to match a foreighn molecule.
2. They bind specifically to the antigen that induced their formation.
There are 5 classes
1. IgG
  1. 4 subclasses of ɣ1-ɣ4 H chains
    1. IgG1
      1. 70% of normal IgG serum in humans
    2. IgG2
      1. 20% of normal IgG serum in humans
    3. IgG3
      1. 8% of normal IgG serum in humans
    4. IgG4
      1. 2% of normal IgG serum in humans
    5. In a mouse these are IgG1, IgG2a, IgG2b and IgG3
  2. 75% of normal serum. Ig 12mg/ml
  3. Basic monomer structure
  4. Mr 150,000 - Can get out of the serum more easily than IgM. Can get to the tissues and so provides immunity for most of the body.
  5. Performance
    1. Predominant Ab of secondary immune response
    2. Extravascular - good at giving protection throughout your tissues.
    3. Fixes complement IgG3>1>2>4 (IgG2 and 4 very weak at fixing complement)
    4. Good opsonin
    5. Placetal transfer IgG1, 3 and 4. Immunity for an unborn child
  6. Where do they bind?
    1. IgG binds to special Fc receptors on lymphocytes, monocytes and macrophages.
2. IgM
  1. µ Heavy chain
  2. Makes up 10% of normal human serum Ig 1.8mg/ml
  3. Pentamer composed of 5 basic Ig monomers
    1. There it has 10 antigen binding sites.
    2. Mr 970,000
    3. 10 L chains (identical), 10 H chains (identical), means there are 10 identical antigen binding sites. There is 1 J chain.
    4. monomers are joined by disulphide bonds.
  4. Performance
    1. Predominant Ab of the primary immune response (on first encounter, you produce IgM)
    2. Most efficient complement fixing antibody
      1. makes holes in cell/pathogen membranes
      2. Sticks things to the pathogen surface to be detected and engulfed by macrophages.
    3. Good opsonin
      1. coats the pathogen so they can be phagocytosed
    4. Half life 5 days
    5. not found extravascularly
      1. Cannot really get out of the serum because of its size. This is a limitation as it can't reach the tissues.
    6. Found at B lymphocyte cell surface as a membrane bound monomer. Here it acts as a cell surface receptor in antigen recognition. Consists of 2 L and H chains. This property is shared with IgD.
3. IgA
  1. 2 subclasses: α1 and α2 heavy chains.
  2. 10% of normal serum
  3. it is mainly monomeric in normal serum
  4. Mr 160,000
  5. Predominant Ig in secretions eg saliva and colostrum and in the gut where it is present as a dimer (of two Ig monomers, one J chain and one secretory component polypeptide.
    1. also found in the lungs, eyes and on our skin.
    2. Secretory component wrapped around the molecule to protect against digestion.
      1. J chain links and holds the chains together
4. IgD
  1. δ heavy chain
  2. Very low levels in serum (at least 1000 fold lower than IgG
  3. Basic monomer structure
  4. Mr 175-185,000
  5. often co-expressed with IgM
  6. Acts in signal transduction following antigen binding leading to B cell proliferation
5. IgE
  1. ε heavy chain
  2. Lowest serum concentrations of any immunoglobulin 0.0003 mg/ml
  3. Basic monomer structure
  4. Mr 190,000
    1. However heavy chain consists of 5 domains
  5. Binds to Fc receptors (specific to IgE) on mast cells and basophils. Contact with antigens subsequently leads to the release of pro-inflammatory agents
  6. Major player in allergy responses and worm infections
Basic Structure
1. Y shaped molecule
  1. 2 identical light chains either λ or K (never one of each) ~ 220AA
  2. Two identical heavy chains ~ 450AA
    Annotations:
    - AA=amino acids
  3. Covalent and non covalent forces hold it together
  4. There are two identical antigen binding sites (labelled Ag in the picture).
    1. will bind to exactly the same antigen (specific)
2. How did immunologists first study this molecule?
  1. Broke down the structure into its functional parts.
    1. Cleaving using...
      1. PAPAIN
        Cleaves polypeptide to the left of the disulphide bond (this bond holds the two heavy chains together). Splits the antibody into two fragments, Fab and Fc.
      2. PEPSIN
        Cleaves polypeptide to the right of the disulphide bond, antibody arms still bound together which is called F(ab')2 fragment and has the Fc fragment left over. The Fc fragment is the carboxy half and is called the Fc region because it is crystallisable.
3. Where are they different?
  1. there are 3 regions of variability and these are called HVR. They are positioned at 30, 50 and 90 AA
    1. The CDR makes up the shape of the antigen binding site
      1. The FDR holds the domains together.
        β regions are the FDRs. At the ends of these are the CDRs. There are 3 CDRs in the light chain and three in the heavy chain.
  2. They need to have the correct forces in order to have high affinity
4. Not all antibodies of different species have two binding sites.

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	Created by Lisa Tang almost 9 years ago