Prediction of protein antigenic determinants from amino acid sequences.

TLDR

The point of highest local average hydrophilicity is invariably located in, or immediately adjacent to, an antigenic determinant. A method is presented for locating protein antigenic determinants by analyzing amino acid sequences to find the point of greatest local hydrophilicity. The method assigns each amino acid a hydrophilicity value, repeatedly averages these values along the peptide chain, and was developed using 12 proteins with extensive immunochemical analysis to predict determinants in various viral, bacterial, and allergenic proteins. Prediction success depends on averaging group length, with hexapeptide averages yielding optimal results, and the hepatitis B surface antigen sequence synthesized chemically was shown to have antigenic activity by radioimmunoassay.

Abstract

A method is presented for locating protein antigenic determinants by analyzing amino acid sequences in order to find the point of greatest local hydrophilicity. This is accomplished by assigning each amino acid a numerical value (hydrophilicity value) and then repetitively averaging these values along the peptide chain. The point of highest local average hydrophilicity is invariably located in, or immediately adjacent to, an antigenic determinant. It was found that the prediction success rate depended on averaging group length, with hexapeptide averages yielding optimal results. The method was developed using 12 proteins for which extensive immunochemical analysis has been carried out and subsequently was used to predict antigenic determinants for the following proteins: hepatitis B surface antigen, influenza hemagglutinins, fowl plague virus hemagglutinin, human histocompatibility antigen HLA-B7, human interferons, Escherichia coli and cholera enterotoxins, ragweed allergens Ra3 and Ra5, and streptococcal M protein. The hepatitis B surface antigen sequence was synthesized by chemical means and was shown to have antigenic activity by radioimmunoassay.