CANONICAL V-H CDR1 NUCLEOTIDE-SEQUENCES ARE CONSERVED IN ALL JAWED VERTEBRATES

The antibody combining site is formed from the complementarity-determi ning regions (CDR) of the heavy and light chains, Function, in antibod ies, means diverse structures capable of binding a variety of ligands and the CDR have long been distinguished as the sites of a high incide nce of non-homologous replacement, The present studies show, despite t he apparent protein diversity, the existence of canonical nucleotide s equences in the heavy chain CDR1. These sequences were deduced from hu man and mouse CDR1, and their presence demonstrated experimentally in all representatives from the gnathostome vertebrate classes. This unex pected conservation suggests that selection pressure for sequence dive rsity is counter-balanced by properties of the encoded amino acids suc h as capacity for ligand interaction, structural requirements of the C DR loop and perhaps retention of certain ligand-binding sequences, Par t of the canonical nucleotide sequence involves a motif that has been suggested as a hot spot for somatic hypermutation. The assay for the c anonical sequence is PCR-based and provides a novel approach to clonin g multigene family members by using the hypervariable portions as targ et sequence.