Conformation-dependent antigenic

Olsnes, S. and Saltvedt, E., 1975. Conformation-dependent antigenic determinants in the toxic lectin ricin, J. Immunol., 114, pp. 1743-1748. 

Structural and antigenic properties of proteins are expected to change after one-electron redox processes whatever they are. Such effect was demonstrated using ovalbumin and bovine serum albumin (226). Antigenicity was decreased by irradiation. This change could be related to that measured by circulary dichroism at 222 nm. The authors suggest that the main part of conformation-dependent antigenic structure is lost by irradiation. 

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. 

Possible effects on soluble protein of immobilization. Protein is shown as having three antigenic sites (epitopes). Two are linear (solid box and shaded pentagon), and one is conformational dependent (shaded oval). 

Fig. 4. Localization of three different types of antigenic determinants in native collagen (a) and denatured collagen, i.e., gelatin (b) (7) helical, conformation dependent (2) terminal, non-helical, conformation independent, low cross-reactivity (5) central, exposed upon de-naturation, conformation independent, high cross-reactivity. (Beil et al. 1973)...

These data suggest that TSST-1 and HI35A share some common epitopes, and a mutation at residue 135 did not greatly alter the conformation of TSST-1. The three dimensional shape of an immunogen is important as most epitopes are conformationally dependent (27). Historically, peptide vaccines have not been very efficacious. This may reflect the inability of most peptides to truly mimic an epitope conformation naturally found on a whole molecule antigen. 

Antigen antibody recognition is dependent on protein structure. A conformational change in a protein caused by formalin fixation may mask the epitope and thus affect the antigenicity of proteins in formalin-treated tissue (Montero 2003). The antigen retrieval leads to a renaturation or at least partial restoration of the protein structure, with re-establishment of the three-dimensional protein structure to something approaching its native condition (Shi et al. 1991). 

In preparation for use as a surrogate vaccine, these peptides were synthesized as conjugates to tetanus toxoid, and in this form also competed with the 0-antigen polysaccharide for binding [104]. Whether these peptides will function as effective immunogenic mimics will likely depend on their propensity to adopt the bioactive conformation in solution. A certain amount... 

---