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Using IMGT unique numbering for IG allotypes and Fc‐engineered variants of effector properties and half‐life of therapeutic antibodies
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Using IMGT unique numbering for IG allotypes and Fc‐engineered variants of effector properties and half‐life of therapeutic antibodies

Marie‐paule Lefranc et Gérard Lefranc
Immunological Reviews, Vol.328(1), p.473-506
04/10/2024
PMCID: PMC11659927
PMID: 39367563

Résumé

allotypes Fc‐engineered variants antibody half‐life antibody‐dependent cellular cytotoxicity antibody‐dependent cellular phagocytosis complement‐dependent cytotoxicity Animals Antibodies, Monoclonal* / classification Immunoglobulin Fc Fragments* / immunology Immunoglobulin Fc Fragments* / metabolism Protein Engineering* Terminology as Topic Antibodies, Monoclonal* / therapeutic use Antibody-Dependent Cell Cytotoxicity* Half-Life Humans Immunoglobulin Allotypes* / classification Immunoglobulin Allotypes* / genetics Immunoglobulin Fc Fragments* / classification Immunoglobulin Fc Fragments* / genetics
Therapeutic monoclonal antibodies (mAb) are usually of the IgG1, IgG2, and IgG4 classes, and their heavy chains may be modified by amino acid (aa) changes involved in antibody‐dependent cellular cytotoxicity (ADCC), antibody‐dependent cellular phagocytosis (ADCP), complement‐dependent cytotoxicity (CDC), and/or half‐life. Allotypes and Fc‐engineered variants are classified using IMGT/HGNC gene nomenclature (e.g., Homo sapiens IGHG1). Allotype names follow the WHO/IMGT nomenclature. IMGT‐engineered variant names use the IMGT nomenclature (e.g., Homsap G1v1), which comprises species and gene name (both abbreviated) followed by the letter v (for variant) and a number. Both allotypes and engineered variants are defined by their aa changes and positions, based on the IMGT unique numbering for C domain, identified in sequence motifs, referred to as IMGT topological motifs, as their limits and length are standardized and correspond to a structural feature (e.g., strand or loop). One hundred twenty‐six variants are displayed with their type, IMGT numbering, Eu‐IMGT positions, motifs before and after changes, and their property and function (effector and half‐life). Three motifs characterize effector variants, CH2 1.6–3, 23‐BC‐41, and the FG loop, whereas three different motifs characterize half‐life variants, two on CH2 13‐AB‐18 and 89–96 with H93, and one on CH3 the FG loop with H115.

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