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Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products.

Ramsland PA, Farrugia W

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  • Journal Journal of molecular recognition : JMR

  • Published 17 Jun 2003

  • Volume 15

  • ISSUE 5

  • Pagination 248-59

  • DOI 10.1002/jmr.585

Abstract

Sequencing of all human immunoglobulin (Ig) germline gene segments has recently been completed. However, our first glimpses of the recombined products of this combinatorial gene system were in the 1970s, in landmark publications, reporting the crystal structures of two human myeloma proteins, the Mcg lambda light chain dimer and the New IgG1(lambda) Fab. Although numerous crystal structures of murine and human antibodies have now been determined, only a relatively small proportion of the human germline genes have had their corresponding protein three-dimensional structures resolved. Therefore, further structural investigations are required before the inherent diversity of the antibody repertoire can be fully appreciated. We discuss the detailed structural information available for human antibodies with regard to their immune functions. Also discussed, is how the structural information is finding application in the 'humanization' of murine antibodies as part of their development as 'biopharmaceuticals' for the treatment of human disease.