title: Specificity, polyspecificity, and heterospecificity of antibody-antigen recognition.
abstract: The concept of antibody specificity is analyzed and shown to reside in the ability of an antibody to discriminate between two antigens. Initially, antibody specificity was attributed to sequence differences in complementarity determining regions (CDRs), but as increasing numbers of crystallographic antibody-antigen complexes were elucidated, specificity was analyzed in terms of six antigen-binding regions (ABRs) that only roughly correspond to CDRs. It was found that each ABR differs significantly in its amino acid composition and tends to bind different types of amino acids at the surface of proteins. In spite of these differences, the combined preference of the six ABRs does not allow epitopes to be distinguished from the rest of the protein surface. These findings explain the poor success of past and newly proposed methods for predicting protein epitopes. Antibody polyspecificity refers to the ability of one antibody to bind a large variety of epitopes in different antigens, and this property explains how the immune system develops an antibody repertoire that is able to recognize every antigen the system is likely to encounter. Antibody heterospecificity arises when an antibody reacts better with another antigen than with the one used to raise the antibody. As a result, an antibody may sometimes appear to have been elicited by an antigen with which it is unable to react. The implications of antibody polyspecificity and heterospecificity in vaccine development are pointed out.
authors.affiliation: Wallenberg Research Center, Stellenbosch Institute for Advanced Study, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Marc H V
authors.initials: MH
authors.lastname: Van Regenmortel
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D022801:Complementarity Determining Regions / Q000737:chemistry*; D006801:Humans
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D022801:Complementarity Determining Regions
keywords: HIV-1 vaccines; antibody specificity; epitope prediction; heterospecificity; monogamous bivalent binding; peptide hydropathic complementarity; polyreactive antibodies; polyspecificity