A V region mutation in a phosphocholine-binding monoclonal antibody results in loss of antigen binding

• Published in: The Journal of immunology (1950) Vol. 146; no. 6; pp. 2017 - 2020
• Main Authors: Kobrin, BJ, Buhl, S, Shulman, MJ, Scharff, MD
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.03.1991; American Association of Immunologists
• Subjects: Amino Acids - physiology; Animals; Antibodies, immunoglobulins; Antibodies, Monoclonal - genetics; Base Sequence; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunoglobulin Variable Region - chemistry; Immunoglobulin Variable Region - genetics; Mice; Mice, Inbred BALB C; Molecular immunology; Molecular Sequence Data; Monoclonal antibodies; Mutation; Phosphorylcholine - immunology; Protein Conformation; Structure-Activity Relationship; Antigen; Binding; Cell line; Gene; Substitution; Deficiency; Variable region; Hybridoma; Molecular interaction; Aspartic acid; Monoclonal antibody; Mutation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.146.6.2017

A V region mutant producing an antibody that had lost the ability to bind phosphocholine was isolated from a hybridoma producing a germline encoded T15 antibody. The mutation resulted in a single aspartic acid to asparagine substitution at residue 95 of the H chain V region. This confirms that the aspartic acid at residue 95 plays a major role in Ag binding. The results also suggest that somatic cell genetic techniques can be used to generate mAb with useful changes in Ag binding.