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.