Q.42 Which one of the combinations of the following statements is true about antibody structure?
P. Limited proteolysis of rabbit IgG with the enzyme pepsin generates two antigen-binding
regions (Fab) and an Fc fragment
Q. Limited proteolysis of rabbit IgG with the enzyme papain generates a single bivalent
antigen-binding region F(ab)2 and peptide fragments
R. The Fc fragment of IgG can self-associate and crystallize into a lattice
S. The F(ab)2 fragment of IgG is composed of both light and heavy chains
(A) P and Q only (B) P and R only
(C) R and S only (D) Q and S only

Unlocking Antibody Structure: Pepsin, Papain Digestion & IgG Fragments Explained

Antibody structure involves precise enzymatic cleavage patterns that generate functional fragments like Fab, F(ab’)2, and Fc. This GATE-style question tests knowledge of rabbit IgG proteolysis and fragment properties, with the correct answer being (C) R and S only.​

Correct Answer Breakdown

Statements R and S are true. The Fc fragment self-associates via CH3 domain interactions to form crystalline lattices, as seen in multiple IgG1 Fc structures. The F(ab’)2 fragment comprises two light chains and VH-CH1 domains from heavy chains, linked by hinge disulfide bonds.​

Statement P Analysis

P is false. Pepsin cleaves IgG below the hinge, yielding one F(ab’)2 (bivalent) and a pFc’ fragment (not intact Fc), unlike papain. This limited proteolysis preserves antigen-binding while removing most Fc functionality.​

Statement Q Analysis

Q is false. Papain digestion above the hinge produces two monovalent Fab fragments and one Fc, not a single bivalent F(ab’)2 with peptides. F(ab’)2 requires pepsin; papain’s Fc remains crystallizable.​

Why R Holds True

Fc fragments from IgG readily dimerize and crystallize due to hydrophobic CH2-CH2 and CH3-CH3 contacts, forming orthorhombic lattices in X-ray studies. This property enables structural biology of effector domains.​

Why S Holds True

F(ab’)2 retains complete light chains (VL-CL) and heavy chain arms (VH-CH1 plus hinge), ensuring bivalent binding. Unlike Fab (one light + VH-CH1), it mirrors native avidity.​