第一章 抗体工程药物【参考】.pptVIP

* * * * * * * * * * * * * * * * * * Figure 9-23. Organization of the k light-chain locus in human germ-line DNA. In a library spread over hundreds of kilobases of DNA, there are about 100 Vk segments, each with a unique sequence. The Vk segments occur in both transcriptional orientations, whereas the five Jk segments and one Ck segment are all in the 5 3 orientation (left to right in the illustration). One Lk-Vkunit is shown expanded. It consists of a promoter at the 5 end (beginning of transcription), an exon encoding a leader peptide (Lk), an intron, an exon encoding the Vk region, and a recognition signal. This signal guarantees that the Vk segment will join to a Jk segment. The arrow shows the orientation of the recognition site. See text for further discussion. [After Paul D. Gottleib, Mol. Immunol. 17:1423.] * Figure 9-25. Organization of heavy-chain gene segments in human germ-line DNA. The heavy-chain locus contains a library of D segments in addition to multiple V and J segments analogous to those in the k light-chain locus. The VH, D, and JH segments have recognition signals (red) that assure proper joining. The small arrows indicate the orientation of the recognition signals. By processes similar to those depicted in Figure 9-24, a D segment first joins to a JH segment with theintervening DNA being deleted; a VH segment then joins the preformed DJH unit, forming the variable region of the heavy-chain gene. Subsequent transcription yields a primary transcript, which is spliced to yield heavy-chain mRNA. The Cm segment encodes the constant region of the m heavy chain, which is found in IgM. Other C segments downstream from Cm (not shown) encode the constant regions of heavy chains in the other Ig classes. * * * * * * * * * * * * * * Mabs are produced in too small of quantities by cells in animals to permit a commercially viable manufacturing process. By fusing antibody-producing B lymphocytes with immortal myeloma cells, it is now possible to provide