# DBT JRF 2020 — Question 102

Exam: DBT JRF 2020 · Section: B · Topic: Immunology · Difficulty: Hard

## Question

A humanised antibody is one in which the

## Options

- **A.** antibody heavy chain is from human and light chain is from mouse
- **B.** antibody heavy and light chains are from human
- **C.** antibody light chain is from human and heavy chain is from mouse
- **D.** complementarity-determining regions (CDRs) are from mouse and the rest is from human

## Answer

Option D

## Explanation

Humanised antibodies are engineered to minimise immunogenicity when used therapeutically in humans. The process (CDR grafting): Take the complementarity-determining regions (CDRs — the three hypervariable loops in $V_H$ and $V_L$ of heavy and light chains that directly contact antigen) from a MOUSE monoclonal antibody. Graft these mouse CDRs into a HUMAN antibody framework (FR) and constant regions. Result: ~95% human sequence, ~5% mouse sequence. Advantages: the therapeutic antibody retains the antigen-binding specificity of the original mouse antibody but is much less immunogenic in humans (reduces human anti-mouse antibody/HAMA response). Examples: trastuzumab (Herceptin), bevacizumab (Avastin), alemtuzumab. Further engineering: fully human antibodies (phage display — abciximab, adalimumab) have no mouse sequence.

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