Epitope discontinuous

FIG. 4.1. Schematic representation of two antibodies reacting with a continuous and a discontinuous epitope of a protein antigen interacting residues are indicated in black. If the individual loops of a discontinuous epitope are able to bind to the antibody paratope on their own, they may be given the status of continuous epitope. The inset shows the three loops of an antibody VH chain which form part of the paratope... 

An antibody directed at the murine epitope of infliximab may develop in patients. A delayed infusion reaction, which occurs 1-2 weeks after infusion, develops in approximately 5% patients who are re-treated with infliximab. Delayed infusion reaction is more common in patients with circulating anti-infliximab antibodies (20-30% of those getting multiple infusions) than in those without the antibodies. These reactions consist of myalgia arthralgia fever rash urticaria and facial, hand, and lip edema. Delayed reactions respond to symptomatic treatment with antihistamines or corticosteroids. Positive antinuclear antibodies (ANA) and anti-dsDNA develop in a small number of patients. Development of a lupus-like syndrome has been reported that resolved after discontinuation of the drug. 

Prediction two groups linear and discontinuous epitopes. A linear (also called... 

Owing to the difficulty of evaluating discontinuous epitopes, most experimentally detected epitopes are linear epitopes. Tools for prediction of linear B-cell epitopes include 3DEX, CEP, and Pepito (26-29). IEDB has collected a list of Web tools for B-cell epitope prediction (http //tools.immuneepitope.org/main/... 

Enshell-Seijffers D, Denisov D, Groisman B et al (2003) The mapping and reconstitution of a conformational discontinuous B-cell epitope of HIV-1. J Mol Biol 334 87-101... 

Sweredoski MJ, Baldi P (2008) PEPITO improved discontinuous B-cell epitope prediction using multiple distance thresholds and half sphere exposure. Bioinformatics 24 1459-1460... 

Anderson PH, Nielsen M, Lund O (2006) Prediction of residues in discontinuous B-cell epitopes using protein 3D structure. Protein Sci 15 2558-2567... 

Bublil EM, Freund NT, Mayrose I et al (2007) Stepwise prediction of conformational discontinuous B-cell epitopes using the Mapitope algorithm. Proteins 68 294-304... 

Moreau V, Granier C, Villard S et al (2006) Discontinuous epitope prediction based on mimotope analysis. Bioinformatics 22 1088-1095... 

Geysen et al. [2] first successfully applied this approach in the multipin system in an on-pin ELISA assay to define a mimotope for a monoclonal antibody directed against a discontinuous epitope on the foot-and-mouth disease virus particle. Later, Houghten et... 

Actually antibodies are either directed against a continuous aminoacid sequence, the continuous epitopes, or a domain which is located on various sites in the aminoacid chain, discontinuous epitopes, or conformational epitopes. Continuous epitopes have served as affinity ligands for antibody... 

Figure 12 Superimposition of an LFA-1 antagonist on the discontinuous epitope of ICAM-1 (pdb-code Ham, protein backbone shown as blue tube), which binds to LFA-1. Residues of the protein indicated in yellow contribute to LFA-1 binding and are mimicked perfectly by the small molecule...

In conclusion, the pentapeptides of the YRLRY-NH2 type appear to represent the discontinuous epitope Tyr-1. Arg-35 and Tyr-36 -NH2 (Plate 14). Incorporation of these residues into appropriately substituted pentapeptides is sufficient to allow interaction, with modest affinity, to NPY rat brain Y2 receptors. Furthermore, they competitively antagonize the NPY-induced increase in cytosolic Ca2+ in the Y1-receptor-mediated HEL cell assay. Importantly, these linear peptides suggested a simple model for a minimum, essential pharmacophore and provided a useful starting point for the design of more potent and selective peptide antagonists. 

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