title: Specificity mapping of human anti-T cell receptor monoclonal natural antibodies: defining the properties of epitope recognition promiscuity.
abstract: The classical concept of antibody binding is defined as an exclusive and high-affinity interaction with one epitope. The emerging reality about antibody combing sites, however, is that some can bind unrelated determinants. The studies presented here define this quality as epitope recognition promiscuity by analyzing the capacity of monoclonal human autoantibodies to bind sets of overlapping peptides duplicating the complete structures of T cell receptor (TCR) alpha and beta chains and immunoglobulin lambda chain. We assessed the binding of these monoclonal antibodies (mAbs) to a set of homologous peptides corresponding to the CDR1 segments of human Vbeta gene products, a major epitope used in the selection of the antibodies. We present data on the binding characteristics of four human mAbs selected for the ability to bind TCR epitopes. These mAbs are IgM molecules with VH and VL sequences in germline configuration, but have diverse VH CDR3 regions. These studies aim to characterize the property of epitope promiscuity and show that the relationship between the binding site and its epitope is a complex interaction and unpredictable from antigen sequence alone. Our results support the conclusion that epitope recognition promiscuity is a genuine feature of antibody and TCR recognition.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Robey
authors.forename: Allen B
authors.initials: AB
authors.lastname: Edmundson
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Schluter
authors.forename: David E
authors.initials: DE
authors.lastname: Yocum
authors.forename: John J
authors.initials: JJ
authors.lastname: Marchalonis
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001665:Binding Sites; D001667:Binding, Competitive; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D000939:Epitopes; D007147:Immunoglobulin Light Chains; D010455:Peptides; D011948:Receptors, Antigen, T-Cell