3.1 Immunoglobulin E (IgE)
Structurally, in agreement with other antibody classes, IgE antibody
comprises two identical light and heavy chains. Each chain is formed of
110 amino acid ”immunoglobulin domains”. Disulfide bonds covalently link
the light and heavy chains. Unlike IgD, IgG and IgA, which have three
constant region domains, the heavy chain is structurally similar to the
μ heavy chain of IgM as it has four constant region domains (Cε1-Cε4,
see Figure 1). Cε3 and Cε4 domains are homologous in both sequence and
quaternary structure to the Cγ2 and Cγ3 domains of IgG antibody
isotype3. IgE can be distinguished from IgG by the
position of its Cε2 domains substituting the hinge region of IgG. The
hinge region of IgE is susceptible to digestion by papain. The two
antigen-binding sites are formed by pairing of the variable region of
light and heavy chains.
IgE is asymmetrically bent at the Cε2-3 linker and folds on itself with
the two Cε2 domains folded back and almost touching the Cε4
domains28-30 (Figure 1.2). Fluorescence resonance
energy transfer (FRET) analysis has revealed that the distance between
N- and C- terminal of IgE is around 10 Å, and that binding of IgE with
its receptor induces conformational changes that increase this distance
considerably.
Immunoglobulin E is central to type I immediate allergic
responses1,3. Several studies have illustrated that
antibody isotype class switching in favour of IgE may occur locally in
the nasal mucosa in allergic rhinitis patients and in lymphatic tissues
adjacent to sites of allergen contact but the precise sites for IgE
production are not yet known5-7,31,32. Elevated
concentrations of IgE antibodies have been demonstrated in target
organs, reaching over ten times more in atopic and allergic individuals
than non-atopics5,7,33,34. IgE antibodies bind with
high affinity to FcεRI (association constant, Ka =
1010 M-1) on mast cells and basophils’ surface.