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The success of monoclonal antibodies in clinical practice is dependent on good design. Finding a suitable target is the most important part as other properties of the antibody can be altered by genetic engineering. Antibodies that target lymphocyte antigens offer less toxic immunosuppressive treatment than currently available drugs and the first monoclonal antibody approved for human use is an immunosuppressive agent for treating rejection of renal transplants. Human trails of monoclonal antibodies to treat septic shock have been done and antibodies are also being developed to target common pathogens such as herpes simplex virus. Although monoclonal antibodies against cancer have been much heralded, their success has been limited by the poor access to the inside of tumours. Treatment of blood cancers has been more successful and a human antibody against B cell malignancies is being clinically tested. As knowledge about natural immune responses and antibody engineering increases many more monoclonals are likely to feature in clinical practice. 相似文献
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An antibody was produced in rabbits against partially purified MIF which was released from the specifically stimulated lymphocytes of tuberculin-hypersensitive guinea pigs. The MIF used as an antigen was fractionated by polyacrylamide gel electrophoresis. The antibody thus prepared was then examined for its specificity for several lymphokines by affinity column chromatography. It was observed that the antibody column adsorbed MIF, but not the other three lymphokines, MCF, NCF, and SRF, indicating a keen specificity of the antibody against MIF. 相似文献
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Studies of a monoclonal antibody to skeletal keratan sulphate. Importance of antibody valency. 总被引:7,自引:0,他引:7
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A mouse monoclonal antibody (AN9P1) to keratan sulphate is described. In a competitive-inhibition solution-phase radioimmunoassay employing 125I-labelled intact proteoglycan, it reacts preferentially with keratan sulphate bound to the core protein of adult human articular-cartilage proteoglycan and to a much lesser degree with keratan sulphate purified from this proteoglycan. Proteolytic cleavage of the proteoglycan by pepsin and trypsin has little effect on antibody binding, but treatment with papain decreases binding considerably and more than does treatment with keratanase. An even greater decrease in binding is observed after treatment with alkaline borohydride. A comparison of binding of antibody AN9P1 with that of another previously described monoclonal antibody, 1/20/5-D-4, to keratan sulphate [Caterson, Christner & Baker (1983) J. Biol. Chem. 258, 8848-8854] revealed similar binding characteristics, both showing much diminished binding after papain digestion of proteoglycan and even less with purified skeletal keratan sulphate. Removal of the Fc piece of antibody AN9P1 had no significant effect on the differential binding of divalent F(ab')2 fragment to proteoglycan, to papain-digested proteoglycan and to keratan sulphate, although there was a small decrease in binding to papain-digested proteoglycan. Conversion of the antibody into univalent Fab fragment with removal of the Fc piece resulted in diminished binding to proteoglycan, compared with that observed with IgG, and in enhanced binding to free keratan sulphate and to papain-digested proteoglycan. These results suggest that close proximity of keratan sulphate chains on the core protein of proteoglycans favours preferential reactivity of bivalent antibody with these species through cross-bridging of chains by antibody. Conversely, much decreased binding to keratan sulphate on proteoglycan core-protein fragments and to free keratan sulphate results from a lack of close proximity of keratan sulphate. By using univalent Fab fragment in these assays these differences in binding are minimized by preventing cross-bridging and thereby enhancing detection of smaller fragments without sacrificing too much sensitivity of detection of larger proteoglycan species. The persistent preferential binding of Fab fragment to proteoglycan is probably in part the result of the increased epitope density in the intact molecule compared with keratan sulphate in a more disperse form. 相似文献
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Y Tai Kim D Greenbaum P Davis S A Fink T P Werblin G W Siskind 《Journal of immunology (Baltimore, Md. : 1950)》1975,114(4):1302-1306
The effect of boosting on antibody affinity was studied in a haptenic system. Generally, boosting results in the prompt synthesis of high affinity anti-hapten antibody. However, repeated boosting frequently leads to a decrease in the amount and affinity of the serum antibody. Repeated boosting with hapten on a carrier different from that used for priming selectively stimulates synthesis of the highest affinity anti-hapten antibody and does not result in a decrease in affinity. Priming with soluble antigen without adjuvants results in the synthesis of low affinity antibody. After such priming, boosting stimulates low affinity antibody synthesis and repeated boosting leads to a moderate increase in antibody affinity. 相似文献
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A knowledge-based three-dimensional model of an anti-insulin antibody, 125, was constructed using the structures of conserved residues found in other known crystallographic immunoglobulins. Molecular modeling and mechanics were done with the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT workstation. A minimal model was made by scaffolding using crystallography coordinates of the antibody HyHEL-5, because it had the highest amino acid sequence homology with 125 (84% light chain, 65% heavy chain). The three hypervariable loop turns that are longer in 125 than in HyHEL-5 (L1, L3, and H3) were modeled separately and incorporated into the HyHEL-5 structure; then other amino acid substitutions were made and torsions optimized. The 125 model maintains all the structural attributes of an antibody and the structures conserved in known antibodies. Although there are many polar amino acids (especially serines) in this site, the overall van der Waals surface shape is determined by positions of aromatic side chains. Based on this model, it is suggested that hydrogen bonding may be key in the interaction between the human insulin A chain loop antigenic epitope and 125. 相似文献
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Studies on the control of antibody synthesis. XVI. Effect of immunodepression on antibody affinity 总被引:1,自引:0,他引:1
The relationship between depression in the magnitude of the immune response and a decrease in affinity of the antibody produced was examined in three different models of immuno-depression (B-cell clonal deletion tolerance, specific suppressor T-cell activity, and anti-genie competition). In B-cell clonal deletion tolerance and in antigen-specific, suppressor T-cell-mediated immunodepression, a small decrease in magnitude (50% or less) is associated with a marked decrease in high-affinity, plaque-forming cells. In contrast, with nonspecific immunodepression, due to antigenic competition, a depression in affinity is only seen when there is a marked (85%) reduction in the magnitude of the response. The results are consistent with the view that when the mechanism of immunodepression involves interaction of antigen with antigen-specific B cells there is a disproportionate loss of high-affinity, antibody-producing cells relative to the decrease in magnitude. In contrast, with nonspecific immuno-depression, where the decrease in affinity is presumably due to inefficient expansion of high-affinity clones, an effect on affinity is only observed in association with a marked depression in the magnitude of the response. 相似文献
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Enhancing antibody. 3. Site of activity 总被引:1,自引:0,他引:1
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