Q.76. Digestion of an immunoglobulin G (IgG) molecule with pepsin will NOT
(A) generate a bivalent antigen binding fragment
(B) generate monovalent antigen binding fragments
(C) destroy the complement binding site
(D) cleave the heavy chain of IgG molecule
Pepsin digestion of immunoglobulin G (IgG) produces specific fragments key to immunology research. The correct answer to the question is option (B), as it does not generate monovalent antigen-binding fragments.
Correct Answer
Digestion of an IgG molecule with pepsin will NOT generate monovalent antigen binding fragments (B). Pepsin cleaves IgG below the hinge region, yielding a bivalent F(ab’)2 fragment and small Fc peptides, preserving the two Fab arms connected by disulfide bonds.
Option Analysis
Pepsin acts as an endopeptidase at acidic pH, targeting heavy chains near the hinge to separate the antigen-binding region from the Fc domain without yielding single Fab units directly.
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(A) Generate a bivalent antigen binding fragment: This occurs, as F(ab’)2 retains bivalency for enhanced avidity minus Fc functions.
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(B) Generate monovalent antigen binding fragments: This does not happen; monovalent Fab requires papain or reduction of F(ab’)2, not pepsin alone.
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(C) Destroy the complement binding site: This is true, since pepsin removes the Fc region containing the complement C1q site.
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(D) Cleave the heavy chain of IgG molecule: Pepsin specifically cleaves heavy chains above the Fc, producing peptides from it.
IgG Structure and Digestion Comparison
| Enzyme | Cleavage Site | Products | Antigen Binding | Complement Binding |
|---|---|---|---|---|
| Pepsin | Below hinge | F(ab’)2 (bivalent) + Fc peptides | Bivalent | Destroyed |
| Papain | Above hinge | 2 Fab (monovalent) + Fc | Monovalent | Intact (Fc preserved) |
This table highlights pepsin’s role in F(ab’)2 production for applications avoiding Fc-mediated effects.
