Presentation of an antibody

Monoclonal antibodies

Monoclonal antibodies (mAbs) and derivatives make up the class of active ingredients that is currently experiencing the greatest rate of development in the biotechnology and pharmaceutical fields. In a little more than thirty years, near than 50 immunoglobulins (IgG) and derivatives have obtained marketing authorizations (MA) for highly varied therapeutic indications (oncology, inflammation and auto-immunity, transplantation, angioplasty, hematology, ophthalmology, viral infections, allergy). The palette of structures includes mouse, chimeric, humanized and human antibodies of different isotypes (IgG1, 2 and 4), as well as IgG derivatives (immunoconjugates, radio-immunoconjugates, Fab fragments, Fc fusion peptides and proteins, mouse/rat bispecifics).

 

Human and mouse IgG are tetrameric glycoproteins that are bivalent (two binding sites to Ag) and bifunctional (binding to Ag and gamma-Fc receptors). These are heterodimers of around 150 kDa made up of two heavy chains (50 kDA ≈ 450 aa) and two light chains (25 kDA ≈ 220 aa). These polypeptide chains are connected by a characteristic number of disulfide bridges (S-S), involved in pairings specific to each isotype. The light chains are made up of a variable domain (VL) and a constant domain (CL); the heavy chain of a variable domain (VH), three constant domains (CH1, 2 and 3) and a hinge region (H, hinge), located between the domains CH1 and CH2. The heavy chains include a N-glycosylation conservation site, generally located on Asn297 (Asn84.4) of the domain CH2 in the IMGT (www.imgt.org) numbering scheme. The variable domains of the heavy and light chains each include three hypervariable regions involved in the specificity of recognition of the Ag (CDR for Complementarity Determining Regions) alternating with framework domains (FR). The very flexible hinge contains the S-S bridges that interconnect the heavy chains. This domain contains a special enzymatic cleavage site (papaine) that can be used to fragment the Acm into Fab (a fragment that binds to the Ag) and Fc (crystallizable fragment), of around 50 kDa each. The Fab is responsible for the specific binding with a strong affinity for the Ag. The Fc fragment binds to y-Fc receptors involved in the effector functions of the Acm (ADCC = antibody-dependent cellular cytotoxicity, CDC = complement-dependent cytotoxicity), as well as to FcRn that give human IgG a plasma half-life of around 20 days.

 

See animation of an antibody

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