Cloning and sequence analysis of κ and γ cynomolgus monkey immunoglobulin cDNAs

One γ heavy chain and 10 κ light chain cynomolgus monkey ( Macaca fasicularis) immunoglobulin cDNAs have been cloned and sequenced. Comparisons of the variable (V) regions to human antibody sequences have revealed extensive identity, exhibiting 93% at the amino acid level for the V H framework regions, and 88–99% for the V κ frameworks. Identification of very few cynomolgus monkey-specific framework region residues suggests a role for cynomolgus monkey antibodies as donators of variable regions to chimeric monoclonal antibodies for utilisation in human therapy with human constant (C) regions. The cynomolgus monkey C κ region exhibited 83% amino acid identity to its human counterpart, and the C γ region was 95, 93, 95, and 95% similar to the human C γ1, C γ2, C γ3, and C γ4 regions, respectively. Evolutionary analysis of the C γ genes, using the silent molecular clock, suggests that the divergence between cynomolgus monkey and human occurred before the time at which the ancestral γ gene diverged into the multiple isotypes observed in humans.