Cognitive features of continuous antigenic determinants.
We sought to identify the features controlling the specificity of antibody recognition and thus gain insights into molecular recognition between proteins in general. A total of 103 epitopes within 63 well-defined antigenic peptides homologous with the relevant antigen sequence were identified. The contribution of each amino acid residue to the antibody binding activity of each epitope was investigated by ELISA testing of complete sets of peptide analogs containing single amino acid replacements. The data are summarized in a replaceability matrix. Some of the high frequency replaceabilities were expected, such as aspartate for glutamate, serine for threonine, etc., but unexpected relationships were also found, such as a high degree of acceptability of methionine as a replacement. Replaceability with a residue of opposite charge was rare. Glycine and tyrosine were frequently of low acceptability, except for glycine as a replacement for alanine. It was found that on average only about four to five amino acid residues in epitopes were required to determine specificity and provide binding energy. Specificity and binding energy were attributed to amino acid side chains rather than main chain atoms. Propensity factors for occurrence of amino acids in antigenic determinants were calculated. The prominence of certain hydrophobic residues as residues critical to recognition by antibody suggests that the molecular surface of an antigen in its combined form with antibody is altered from that occurring in the absence of antibody. Thus, antigenicity is not a static surface phenomenon but depends on the ability of the antigen to undergo rearrangement, supporting the induced fit concept.
Geysen
H M
HM
Department of Molecular Immunology, Commonwealth Serum Laboratories, Parkville, Victoria, Australia.
Mason
T J
TJ
Rodda
S J
SJ
D000596:Amino Acids; D000818:Animals; D000916:Antibody Diversity; D000937:Antigen-Antibody Reactions; D001665:Binding Sites; D000939:Epitopes / Q000145:classification / Q000378:metabolism; D006801:Humans; D007256:Information Systems; D010455:Peptides / Q000276:immunology* / Q000378:metabolism
D000596:Amino Acids; D000939:Epitopes; D010455:Peptides