Antibodies are proteins with two heavy chains and two light chains produced by B cells, central to the adaptive immune system. Their structure consists of a variable region (containing CDRs and a framework region) and three constant regions (CH1, CH2, CH3). The variable region and CH1 form the Fab, while the remainder forms the Fc region. B cell receptors are antibodies with an additional CH4 domain.
Types of antibodies
IgA is found in mucous membranes, cannot activate the complement system, and makes up roughly two-thirds of antibodies in healthy adults. It is notable for being double-sided.
IgE has only one binding site, mainly protects against large organisms like parasites, and is responsible for allergic reactions.
IgG is the standard antibody class used in therapeutic design. Cannot activate the complement system and can pass through the placenta.
- IgG1 makes up 67% of all antibodies in the human body, is capable of antibody-dependent cellular phagocytosis, and has the longest hinge region. IgG1 immune repertoires consist mostly of just a few dozen dominant clones and are unique to each individual, remaining largely stable over time.
- IgG2 — mice have IgG2a and IgG2b instead; some strains have IgG2c instead of IgG2a.
- IgG3 makes up ~7% of IgGs and has a notably shorter half-life due to poor binding to FcRn, attributed to an H435R mutation.
- IgG4 is the rarest IgG and undergoes Fab-arm exchange, dissociating into half-bodies and forming novel combinations via R409 in the hinge. Therapeutic IgG4 antibodies use the S228P substitution to stabilize the hinge and prevent this.
IgM is far less subject to affinity maturation than IgG, responds to lipids and polysaccharides, and activates the complement system.
Datasets
SAbDab is a database of all antibody and nanobody structures in the PDB. The full list can be downloaded with:
curl -s https://opig.stats.ox.ac.uk/webapps/sabdab-sabpred/sabdab/summary/all/