ABSTRACT
Antibodies are capable of highly specific interactions with a wide variety of ligands including tumor-associated markers, viral coat proteins and lymphocyte cell surface glycoproteins. Some of the limitations of monoclonal antibodies as therapeutic agents have been addressed by genetic engineering. Recombinant DNA technology can also be employed to generate human monoclonal antibodies from human lymphocyte mRNA. The first generation of recombinant monoclonal antibodies consisted of the rodent-derived variable regions fused to human constant regions. It is thought that the most immunogenic regions of antibodies are the conserved constant domains. A statistical analysis of unique human and murine immunoglobulin heavy and light chain variable regions revealed that the precise patterns of exposed residues are different in human and murine antibodies, and most individual surface positions have a strong preference for a small number of different residues. The construction of chimeric and humanized antibodies offers the opportunity of tailoring the constant region to the requirements of the antibody.
