Cryptic epitopes

Two processes are suggested to be of importance in the induction of T cell sensitization by chemicals (i) the formation of neoantigens (i.e., cryptic epitopes or hapten-carrier conjugates) (ii) the stimulation of innate immune processes (i.e., adjuvant activity or induction of danger signals reviewed by Uetrecht [64]). The... 

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. 

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... 

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.

Kalluri R, Cantley LG, Kerjaschki D, Neilson EG Reactive oxygen species expose cryptic epitopes associated with autoimmune good pasture syndrome. J Biol Chem 2000 275 20027-32. 

Matsunaga Y, Peretz D, Williamson A, Burton D, Mehlhom I, Groth D, Cohen FE, Prusiner SB, Baldwin MA (2001) Cryptic epitopes in N-terminally truncated prion protein are exposed in the full-length molecule dependence of conformation on pH. Proteins Struct Funct Bioinform 44 110... 

Bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) (reviewed in ref. [51]) or trypanosomal GPI-specific phospholipase C (GPI-PLC) [52-54] releases GPI-anchored proteins from the cell surface leaving behind diacylglycerol. This cleavage not only solubilizes the protein, but also exposes a phosphoinositol-containing cryptic epitope termed cross-reacting determinant [55]. Reactivity of polyclonal antibodies derived against the cross-reacting determinant (CRD) provide additional evidence for the presence of a GPI anchor. 

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). 

T cells. T cells that recognize dominant epitopes with too high an affinity or avidity have a high chance of being eliminated during the intrathymic selection process, whereas T cells that are specific to cryptic epitopes will usually not encounter their epitope in the thymus. Hence, these T cells will not be eliminated in the thymus and appear in the peripheral system. 

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). 

Increase in the expression of MHC class II Modification of the autoantigen Presentation of cryptic epitopes... 

Stijiemans B, Coniath K, Cortez-Retamozo V et al. Effident taigeting of conserved cryptic epitopes of infectious agents by single domain antibodies African trypanosomes as paradigm. J Biol Chem 2004 279 1256-1261. 

Borza D-B, Netzer K-O, Leinonen A, et al. The Goodpasture Autoantigen identification of multiple cryptic epitopes on the NCI domain of the ot3(IV) collagen chain. J Biol Chem 2000 275 6030-6037. 

Borza D-B, Bondar O, Colon S, et al. Goodpasture autoantihodies unmask cryptic epitopes hy selectively dissociating autoantigen complexes lacking structural reinforcement. J Biol Chem 2005 280 27147-27154. 

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