Linear epitope

Key words B-cell epitopes, Linear, Conformational, Support vector machines, Hidden Markov models, Immunoinformatics... 

The most frequent application of SPOT-synthesis has been in the preparation of peptide arrays for the identification of linear B-cell epitopes. If the protein antigen is known, a set of overlapping peptides that encompass the entire sequence can be readily synthesized and assayed for binding of antibody (Reineke et al., 1999). The individual residues critical for binding can then be determined by SPOT-synthesis of peptides containing amino acid substitutions. 

Figure 7.2 Schematic showing the relationship of the native antigen to the peptide mimic. The native antigen (a protein) is shown as a winding, twisted line, so as to represent a hypothetical three-dimensional structure. The peptide represents the antibody-binding epitope (shown in dotted lines) of the native antigen. The epitope can represent a linear sequence of the native protein. Alternatively, the epitope can be formed by amino acids that are not immediately adjacent to each other in the primary sequence but brought together by the three-dimensional folding of the protein. Adapted with permission from Sompuram et al.6...

If a monoclonal antibody was generated by immunization with a full-length native protein rather than a peptide, then the immunized mouse will generate antibodies that recognize both linear and conformationally dependent epitopes. Only a small subset of these monoclonal antibodies will likely be useful for clinical use on formalin-fixed, paraffin-embedded tissue (FFPE) samples. Those that are useful tend to have epitopes that are linear the epitopes are not dependent on the protein s three-dimensional conformation (see Chapter 16). Therefore, for antibodies generated in response to immunization with full-length proteins, the peptides that serve as positive controls will be linear stretches of amino acids derived from the native protein sequence, as listed in protein databases. 

Sompuram SR, Vani K, Hafer LJ, et al. Antibodies immunoreactive with formalin-fixed tissue antigens recognize linear protein epitopes. Am. I. Clin. Pathol. 2006 125 82-90. 

A MODEL OF ANTIGEN RETRIEVAL REQUIRING LINEAR EPITOPES... 

Augstein P, Ziegler B, Schlosser M, et al. Immunohistochemical differentiation of monoclonal GAD antibodies recognizing linear or conformational epitope regions. Pancreas 1997 15 139-146. 

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