Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products
β Scribed by Paul A. Ramsland; William Farrugia
- Book ID
- 102373297
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 388 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0952-3499
- DOI
- 10.1002/jmr.585
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β¦ Synopsis
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 Ξ» light chain dimer and the New IgG1(Ξ») 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 threeβdimensional 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 βhumanizationβ of murine antibodies as part of their development as βbiopharmaceuticalsβ for the treatment of human disease. Copyright Β© 2002 John Wiley & Sons, Ltd.
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The crystal structures of two pairs of Fab fragments have been determined. The pairs comprise both a murine and an engineered human form, each derived from the antitumor antibodies A5B7 and CTM01. Although antigen specificity is maintained within the pairs, antigen affinity varies. A comparison of t