Cryptic antigens

Another critical determinant in the cascade of events leading to MS lesion development is antigen presentation. Antigen presenting cell (APC)/T-cell activation involves at least four major processes (1) Molecular mi mi cry, (2) Epitope spreading, (3) Bystander activation, and (4) Cryptic antigen... 

Bystander activation activation of autoreactive cells through nonspecific inflammation and induction of inflammatory cytokines and chemokines is also of pathological consequence in MS. It has been suggested that bystander activation, induced by persistent virus infection or primed by molecular mimicry may activate autoreactive T-cells specific for the CNS (McCoy et al., 2006). Einally, cryptic antigens may also play a role in immune activation. In other immune-mediated diseases such as Chronic Lymphocytic Thyroiditis and Chagas Heart Disease, exposure of cryptic epitopes leads to the activation of autoimmune cells and further contributes to... 

The only internationally used drug effective for treating schistosomiasis is praziquantel. This drug induces a rapid influx into the worms of surrounding Ca2+, a process that leads to paralysis (Martin, 1997), and changes in the surface membrane architecture that lead to the exposure of worm antigens that are normally cryptic (Brindley and Sher, 1987). Parasites affected in this way become susceptible to antibody-mediated immune attack and are killed as a result of the synergistic actions of chemotherapy and the immune response (Doenhoff et al., 1987 Brindley etal., 1989). 

PAb 240, DO-11, and DO-12 antibodies do not precipitate all of the mutant p53 proteins, suggesting that in some mutant molecules the epitopes remain cryptic. Cryptic epitopes can be exposed by denaturation or through mutations. PAb 240 antibody can be used for wild-type and mutant p53 proteins on fresh or paraffin-embedded tissues with the aid of an appropriate antigen retrieval method. Because PAb 240 reacts with a conformational-dependent epitope in the p53 molecule, this antibody has helped define the occurrence of different conformational forms of the p53 protein. 

Skurnik, M., Peippo, A., Ervela, E. Characterization of the O-antigen gene clusters of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Yersinia pestis shows that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O lb. Mol Microbiol 37 (2000) 316-330. 

DeVries GH (2004) Cryptic axonal antigens and axonal loss in multiple sclerosis. Neurochem Res 29 1999-2006. 

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.

Griem P, Panthel K, Kalbacher El, Gleichmann E Alteration of a model antigen by Au(lll) leads to cell sensitization to cryptic peptides. EuR. J. Immunol. 1996 26 279-287. 

Non-tolerant epitopes can be defined as parts of antigenic selfproteins to which no tolerance has developed and to which an immune response can take place when recognized by T lymphocytes. Examples of non-tolerant epitopes are sequestered epitopes and cryptic epitopes (Sercarz et al., 1993 Moudgil Sercarz, 1994). 

Iron. Vital metal for the proliferation of all cells including those of the immune system. May be involved in the induction of autoimmunity by influencing the antigen presentation (catalysing the production of cryptic epitopes of autoantigens). 

Sercarz EE, Lehmann PV, Ametani A, Benichou G, Miller A, Moudgil K (1993) Dominance and crypticity of T cell antigenic determinants. Annu Rev Immunol, 11 729-766. 

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