Cloning and sequence analysis of kappa and gamma cynomolgus monkey immunoglobulin cDNAs

Abstract

One gamma heavy chain and 10 kappa light chain cynomolgus monkey (Macaca fascicularis) 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 VH framework regions, and 88-99% for the V kappa 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 kappa region exhibited 83% amino acid identity to its human counterpart, and the C gamma region was 95, 93, 95, and 95% similar to the human C gamma 1, C gamma 2, C gamma 3, and C gamma 4 regions, respectively. Evolutionary analysis of the C gamma genes, using the silent molecular clock, suggests that the divergence between cynomolgus monkey and human occurred before the time at which the ancestral gamma gene diverged into the multiple isotypes observed in humans.