Each antibody format trades molecular weight for reach: a full IgG (150 kDa) is bivalent and carries an Fc tail that recruits immune effector cells, while Fab, scFv and nanobody fragments are smaller, monovalent and diffuse faster but cannot trigger Fc-mediated killing on their own. Binding to the target cell's surface antigen follows a Langmuir-style equilibrium set by the dissociation constant Kd — the antibody concentration at which half the receptors are occupied.
θ = C / (C + Kd) (fraction of receptors occupied)
D ∝ 1 / √MW (diffusion speed vs molecular weight)
risk ≈ (100 − humanization) × 0.8% (illustrative immunogenicity)
- Format — sets molecular weight, valency (1 or 2 binding arms) and whether an Fc domain is present; smaller fragments diffuse faster but only IgG can trigger ADCC.
- Humanization — the share of the framework replaced with human sequence via CDR grafting; more human framework lowers immunogenicity risk (shown in the red→blue tint of each arm).
- Affinity maturation — phage-display-style CDR optimisation that lowers Kd (tighter binding), raising equilibrium receptor occupancy on the target cell.
- Enhanced ADCC — engineered Fc mutations that boost effector-cell recruitment; only available on the bivalent IgG format, it spawns NK cells that dock on occupied receptors and clear them.
Real-world relevance: this is why therapeutic antibodies are engineered as a bundle of trade-offs — nanobodies penetrate tissue fastest but can't recruit effector cells, while a fully humanized, affinity-matured IgG with an engineered Fc combines low immunogenicity, tight binding and cell-killing power, at the cost of size and manufacturing complexity.