Canonical VH CDR1 nucleotide sequences are conserved in all jawed vertebrates

The antibody combining site is formed from the complementarity-determining regions (CDR) of the heavy and light chains. Function, in antibodies, means diverse structures capable of binding a variety of ligands and the CDR have long been distinguished as the sites of a high incidence os non-homologous replacement. The present studies show, despite the apparent protein diversity, the existence of canonical nucleotide sequences in the heavy chain CDR1. These sequences were deduced from human and mouse CDR1, and their presence demonstrated experimentally in all representatives from the gnathostome vertebrate classes. This unexpected conservation suggests that selection pressure for sequence diversity is counter-balanced by properties of the encoded amino acids such as capacity for ligand interaction, structural requirements of the CDR loop and perhaps retention of certain ligand-binding sequences. Part of the canonical nucleotide sequence involves a motif that has been suggested as a hot spot for somatic hypermutation. The assay for the canonical sequence is PCR-based and provides a novel approach to cloning multigene family members by using the hypervariable portions as target sequence.