Comparative sequence analysis of CO17-1A antigen-specific monoclonal antibodies

Sequence analysis of murine monoclonal antibodies (MAbs) specific for the CO17-1A antigen is being performed to assess the structural basis for antibody specificity for this antigen. Preliminary data reveal that the heavy chain variable regions of MAbs GA733 and CO17-1A (designated Ab1s since they were isolated following immunization with CO17-1A antigen) most likely utilize distinct members of the same gene family. Remarkably, they also display identical amino acid sequences in their heavy chain CDR3 regions, reflecting absolute nucleotide sequence identity across their VH-D-JH junctions. Since these junctional sequences are randomly generated during the assembly of immunoglobulin genes and in general display enormous diversity, this homology suggests an important role for heavy chain CDR3 in determining specificity for the CO17-1A antigen in these antibodies.