Exquisite specificity and peptide epitope recognition promiscuity, properties shared by antibodies from sharks to humans.
This review considers definitions of the specificity of antibodies including the development of recent concepts of recognition polyspecificity and epitope promiscuity. Using sets of homologous and unrelated peptides derived from the sequences of immunoglobulin and T cell receptor chains we offer operational definitions of cross-reactivity by investigating correlations of either identities in amino acid sequence, or in hydrophobicity/hydrophilicity profiles with degree of binding in enzyme-linked immunosorbent assays. Polyreactivity, or polyspecificity, are terms used to denote binding of a monoclonal antibody or purified antibody preparation to large complex molecules that are structurally unrelated, such as thyroglobulin and DNA. As a first approximation, there is a linear correlation between degree of sequence identity or hydrophobicity/hydrophilicity and antigenic cross-binding. However, catastrophic interchanges of amino acids can occur where changing of one amino acid out of 16 in a synthetic peptide essentially eliminates binding to certain antibodies. An operational definition of epitope promiscuity for peptides is the case where two peptides show little or no identity in amino acid sequence but bind strongly to the same antibody as shown by either direct binding or competitive inhibition. Analysis of antibodies of humans and sharks, the two most divergent species in evolution to express antibodies and the combinatorial immune response, indicates that the capacity for both exquisite specificity and epitope recognition promiscuity are essential conserved features of individual vertebrate antibodies.
Marchalonis
J J
JJ
Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, Arizona, USA. diannah@u.arizona.edu
Adelman
M K
MK
Robey
I F
IF
Schluter
S F
SF
Edmundson
A B
AB
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D001323:Autoantibodies; D001666:Binding Sites, Antibody; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell; D012754:Sharks / Q000276:immunology*; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000941:Antigens; D001323:Autoantibodies; D018985:Epitopes, B-Lymphocyte; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D010455:Peptides; D011948:Receptors, Antigen, T-Cell