Q.6 A humanized antibody is one in which the
(A) heavy and light chains are from human
(B) heavy chain is from human and light chain is from mouse
(C) light chain is from human and heavy chain is from mouse
(D) CDRs are from mouse, and the rest is from human

Humanized antibodies contain mouse complementarity-determining regions (CDRs) grafted onto a human framework to reduce immunogenicity while preserving antigen specificity, making (D) the correct answer. This technique revolutionized therapeutic monoclonal antibody development.​

Correct Answer

The correct option is (D) CDRs are from mouse, and the rest is from human. CDR grafting transfers the six hypervariable loops (three per variable domain) from murine antibodies into human heavy/light chain frameworks, minimizing HAMA responses. Framework back-mutations may optimize binding and stability.​

Option Explanations

Humanization progresses from chimeric (murine V regions, human C) to humanized (murine CDRs only), reducing ~90% non-human content.

• (A) Heavy and light chains are from human: Incorrect; describes fully human antibodies from phage display or transgenic mice, not humanized.​

• (B) Heavy chain from human, light from mouse: Incorrect; no standard designation; mixed chains lose therapeutic rationale.​

• (C) Light chain from human, heavy from mouse: Incorrect; similarly non-standard; humanization affects both V regions symmetrically.​

• (D) CDRs from mouse, rest from human: Correct; retains antigen-binding specificity (~5% murine) in human scaffold for prolonged half-life.​

Mechanism Overview

Murine mAbs identify CDRs via sequencing, select homologous human germlines, graft CDRs, and refine via mutagenesis. Examples include Herceptin (trastuzumab): mouse CDRs in human IgG1 framework targets HER2 in cancer. Success rate improved from 50% (early 1990s) to >90% with computational design.​