Disease-specific epitopes

The studies to use phage display to define disease-specific epitopes, in infections and autoimmune disease (e g. Refs. 17 and 61), without knowing the specific antigens involved are exciting possibilities which are at present difficult to evaluate. 

The same may hold true for the different stages in endothelial cell activation during flare-ups in chronic inflammatory disorders. Therefore, the use of a combination of different drug targeting preparations aimed at disease stage-specific epitopes is likely to be a prerequisite for targeting endothelial cells at various stages of activation. 

Hoffmann, R., Lee, V.M.Y., Leight, S., Varga, I., and Otvos, L Jr. (1997) Unique Alzheimer s disease paired helical filament specific epitopes involve double phosphorylation at specific sites. Biochemistry 36, 8114-8124. 

Mariea M, Mezo G, Hudecz F, Przybylski M (2004) Polypepdde conjugates comprising a beta-amyloid plaque-specific epitope as new vaccine str uctures against Alzheimer s disease. Biopolymers 76 503-511. 

Examples 4 and 5 show the use of a polyclonal serum to either capture or detect. As a capture serum, mAbs can be used to detect specific epitopes and increase the specificity of assays. Again, with antigens showing limited epitopes, the polyclonal capture may result in prevention of any more binding saturation of epitopes. When polyclonal antibodies are used as a general detector, they allow a number of mAbs to be screened for effective capture of antigens. The specificity of the initial capture depends on the mAb. Here, orientation effects are more limited (as shown in data, e.g., with foot-and-mouth disease virus (FMDV) in Subheading 10.1). 

To evaluate the potential correlation between specific epitopes on B lipoprotein subpopulations and predisposition to coronary artery disease, recently we have quantitated lipoprotein particles recognized by three well-characterized monoclonal antibodies in normal and CAD patients. 

Hypersensitivity to foreign epitopes Anti-idiotypic response to normal cells Immune complex disease Potential MPS toxicity D. Specific specificity... 

Rabbit hemorrhagic disease vims VP60 epitope Epitope display on plum pox potyvirus in tobacco leaf Rabbits developed specific antibodies that showed neutralizing activity. Immunogenic when delivered to mice parenterally immunogenic in rabbits when delivered parenterally. Rabbits immunized parenterally survived lethal challenge. 78, 84... 

Foot and mouth disease virus VP1 epitope Potato FMDV-VPl-specific antibody response. Immunogenic. Protective against challenge. 22... 

Foot and mouth disease virus VP1 epitope Alfalfa leaf Mice developed specific antibody response to synthetic peptide,VP1 epitope, and intact FMDV particle. Immunogenic in mice when administered parenterally or orally. Mice protected against challenge with FMDV vims. 21, 23... 

Rabbit hemorrhagic disease virus VP60 epitope Potato leaf VP60 specific antibodies elicited in rabbits. Immunogenic in rabbits when administered parenterally. Rabbits protected when challenged with virulent RDHV. 67... 

The mechanism most commonly invoked to explain the association of infection with autoimmune disease is molecular mimicry that is, the concept that antigens (or more properly, epitopes) of the microorganism closely resemble self-antigens.50 The induction of an immune response to the microbial antigen thus results in cross-reactivity with selfantigens and the induction of autoimmunity. Although epitope specific cross-reactivity has been shown in some animal models,48,51 53 molecular mimicry is clearly demonstrated to be the causative mechanism in few, if any, human diseases.3 54,55... 

There is considerable interest in the role of infectious agents in the development of autoimmune diseases. Some of this interest is based on the concept of molecular mimicry as a causal mechanism. Molecular mimicry refers to the possible pathologic role of cross-reactive antibodies or T cells to a self-antigen that is structurally similar to, and thus shares epitopes with, a viral or other infectious agent. For most autoimmune diseases, however, evidence of molecular mimicry leading to disease is not conclusive.1819 Viruses and other infections also have a less-specific immune effect, stimulating toll-like receptors and proinflammatory cytokine secretion, which is another mechanism that has been postulated to influence autoimmune disease risk.20... 

Adjuvants enhancing HLA class I-restricted CTL responses are especially needed for treatment or prevention of chronic viral diseases and infections linked to intracellular pathogens, and for cancer immunotherapy. Among the very few adjuvants licensed for human use, we evaluated the capacity of IRIV to enhance HLA class I-restricted CTL responses in vitro. We addressed IRIV-elicited immune responses and the induction of CTL specific to IM58 66 and Melan-A/Mart-127-35 epitopes. Proliferation assays, cytokine expression studies, and phenotypes of CD4+ T-cells demonstrated that IRIV... 

Table 9.1. Epitopes on pro-angiogenic vascnlar endothelinm that may differentiate between healthy and diseased vascnlatnre and therefore be snitable for drng targeting or diagnostic purposes. Target epitopes presented by molecules specific for tumour-associated basement membrane, extracelliiar matrix or non-endothelial cell components have not been included.

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