Autoimmune antibody-antigen interactions

Xu et al. [5] described the effect of (z>)-penicillamine on the binding of several antiacetylcholine receptor monoclonal antibodies to the Torpedo acetylcholine receptor. Penicillamine is covalently incorporated into the acetylcholine receptor through SS exchange at the cysteine residues of the a-subunit, altering the antigenic structure of the receptor. This effect on the structure of the native receptor at the neuromuscular junction may be responsible for the establishment of the autoimmune response to the acetylcholine receptor in (i))-penicillamine-induced myasthenia gravis. Cysteine and penicillamine interact to form penicillamine-cysteine mixed disulfide complexes [6] ... 

Antigen arrays, also described as reverse-phase protein arrays (Paweletz et al., 2001), involve the immobilization of proteins to serve as bait for various protein-protein interactions (Sreekumar and Chinnaiyan, 2002). For example, Joos et al. (2000) printed down various autoantigens present in sera with known associations with various autoimmune diseases such as Graves disease lupus connective tissue disease, and others. The group then screened various sera for the presence of autoantibodies. By immobilizing on the array a serial dilution series for each antigen, the titers for these antibodies could be determined. 

Figure 3. Effects of heavy metals (Hg andAu) on Immune cells. Hg was described as able to interact with the nuclear antigen fibrillarin which was assumed to cause a T-cell response against this modified autoantigen. True autoreactive T-ceiis specific for the native antigen were detected in a second time. Hg was shown to induce the expression of a normally cryptic epitope of RNAse A leading to the activation of specific T-cells. However the relevance of this mechanism in terms of induction of autoimmunity has not been demonstrated. Hg orAu have also been shown to poiyctonaity activate T-cells mimicking the effects of stimulation with anti-TCR antibodies. This results in an increase in intracellular Ca concentration, MAP kinase activation and cytokine expression.

Nevertheless, the potential for autoimmune disease would clearly exist if one considers the polyspecificity of immune recognition molecules such as B cell receptors, antibodies, T cell receptors and MHC molecules. Further, the polyspecificity of immune receptors is also able to transcend the biochemically defined classes of biomolecules. For instance, the monoclonal antibody SYA/J6 has been demonstrated to have a dual specificity, binding a specific carbohydrate or a specific peptide with comparable affinity.68 Detailed analysis of the interatomic interactions between the antibody combining site and either the carbohydrate or the peptide antigens demonstrated that functional mimicry is possible without exact structural mimicry. This example underlines the case that it is not possible to predict with certainty whether the molecular surfaces of all potentially cross-reactive epitopes, whether of foreign or self molecules, will, or will not, be able to bind to a specific antibody. 

Complement system. A group of serum proteins with the capacity to interact with each other when activated. The chain reaction of the activated complement components results in formation of a lytic complex and several biologically active peptides of low molecular weight (anaphylatoxins). The system can be activated by antigen-antibody complexes (classical pathway) and by other components, e.g. bacteria (alternative pathway). As an effector mechanism of the humoral immune response, the activated complement system facilitates opsonization, phagocytosis, and lysis of cellular antigens. Some defects in components of complement are associated with autoimmune diseases (see complement deficiency). 

Sis Lupus. SLE is a multisystem disease of unknown origin characterized J by inflammation related to the presence of autoantibodies in the blood. These autoantibodies react with antigens normally found in the nucleus, cytoplasm, and plasma membrane of the cell. Such self antigen-antibody (autoimmune) interactions initiate an inflammatory cascade that produces the broad symptom profile of multiorgan dysfunction found in Sis Lupus. 

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