Recent Developments with B-Cell Epitope Identification for Predictive Studies

This review discusses currently available methods for predicting B-cell epitopes on proteins. The use of animals for assessing protein immunogenicity is addressed primarily to highlight the differences in B- and T-cell epitope recognition between species. These differences have to be considered when interpreting potential B-cell epitopes identified by the methods addressed here. "In vitro alternatives" focuses on the strengths and limitations of peptide-based technologies. Three types of computer-based methods for identifying potential B-cell epitopes are discussed: (i) methods applying physico-chemical and structural propensity scales for predicting linear epitopes from the primary structure of a protein, (ii) comparative methods basing prediction upon amino acid sequence and structural similarities between antigenically known and unknown proteins, and (iii) a method combining structural features with a B-cell epitope motif database for predicting linear and conformational antigenic determinants. With respect to human safety, the usefulness of antibody-based tests is limited to comparative studies between an antigenically known protein and variants thereof. Similarly, computer-based methods using data mining can address similarities in B-cell epitope profiles between related proteins, if a proper cut off can be defined for the minimal amino acid sequence similarity required for obtaining an acceptable accuracy. Among the physico-chemical and structural scales, scales identifying in a protein hairpin and non-specific turns seem useful for predicting epitopes with a continuous primary binding site. When conformational epitopes have to be identified as well, a novel computer-based tool seems to be the most promising alternative to X-ray crystallography. However, both methods remain to be extensively evaluated and validated. Thus, promising tools for B-cell epitope identification have been developed. But, no validated method for B-cell epitope identification on antigenically unknown proteins is available yet.