title: Antigenic determinants reacting with rheumatoid factor: epitopes with different primary sequences share similar conformation.
abstract: Polyclonal or monoclonal human IgM rheumatoid factors (RF) react with eight antigenic sites on the CH3 IgG domain, four sites on CH2 and two on human beta 2-microglobulin. All 14 of these RF-reactive epitopes are linear 7-11 amino acid peptides with different primary sequence. We questioned whether RF reactivity with such a variety of epitopes showing no obvious sequence homology might result from conformational similarities shared by various RF-reactive regions. Strong support for this concept was obtained using rabbit antisera as well as mouse mAbs to individual CH3, CH2 or beta 2m RF-reactive peptides. Major cross-reactivity was demonstrated between most of the 14 different CH3, CH2, or beta 2m RF-reactive peptides using individual anti-epitope antibodies. Molecular modelling studies of these peptides showed striking similarities in three-dimensional shape among many RF-reactive peptides. Main-chain atoms rather than side chains seemed to contribute most directly to conformational similarity. Molecular simulation studies on control peptides showed no conformational similarities with RF-reactive peptides. Our studies indicate that autoantibodies such as RF recognize main-chain conformations of reactive epitopes and react with a number of antigenic determinants of quite different primary sequence but similar main chain conformations.
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville 32610, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Williams
authors.forename: C C
authors.initials: CC
authors.lastname: Malone
authors.forename: A S
authors.initials: AS
authors.lastname: Kolaskar
authors.forename: U
authors.initials: U
authors.lastname: Kulkarni-Kale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011817:Rabbits; D012217:Rheumatoid Factor / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D012217:Rheumatoid Factor