The IgG or Antibody molecule is a large, roughly ‘Y’ shaped molecule, composed of two types of polypeptide chains, a 50KDa heavy (H) chain and a 25KDa light (L) chain. Each IgG molecule consists of two heavy chains and two light chains. The heavy chains are linked to each other by disulphide bonds and each heavy chain is linked to a light chain by disulphide bonds. The two heavy chains and two light chains of each IgG molecule are identical to each other.
The light chain is made up of two domains, each folded into a structure known as the immunoglobulin fold. The immunoglobulin fold is a structure that is mimicked by many other molecules. It essentially consists of two sheets of anti-parallel β-strands folded in a Greek-Key motif and sandwiched together.
The variability in the sequence of the light chain is mainly limited to the first domain, also known as the Light chain Variable domain (VL). The other domain is known as the Light chain Constant domain (CL). The heavy chain is made up of one Variable domain (VH) and three Constant domains (CH1, CH2 and CH3).
The Variable Domains of the Light and Heavy chains (VL and VH) fold together to make up the Variable region of the IgG molecule and confer on it its antigen binding specificity. The VL and VH and CL and CH1 domains fold together to make up the Fab or antibody binding fragment of the molecule. The CH2 and CH3 domains of the two heavy chains fold together to form the Fc or crystallizable fragment of the molecule.
Sequence variability is not distributed throughout the Variable domain but is concentrated instead into three hypervariable regions each of the VL and VH domains. These regions are named Hypervariable regions 1 – 3 (HV1, HV2 and HV3). Together, these Hypervariable regions code for hypervariable loops at the tips of the Variable domains. These loops determine the specificity of the IgG molecule and are therefore known as Complementarity Determining Regions (CDR1, CDR2 and CDR3).
IgG has several effector functions including:
- The neutralization of pathogen by coating the pathogen and occupying its bind sites so that it cannot affect cells
- The opsonization of pathogen by marking it for phagocytoses by phagocytes including macrophages
- The recruitment of Complement to lyse pathogen cells
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