ANTIGENIC DETERMINANTS REACTING WITH RHEUMATOID-FACTOR - EPITOPES WITH DIFFERENT PRIMARY SEQUENCES SHARE SIMILAR CONFORMATION

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. W e questioned whether RF reactivity with such a variety of epitopes sho wing no obvious sequence homology might result from conformational sim ilarities shared by various RF-reactive regions. Strong support for th is concept was obtained using rabbit antisera as well as mouse mAbs to individual CH3, CH2 or beta(2)m RF-reactive peptides. Major cross-rea ctivity was demonstrated between most of the 14 different CH3, CH2, or beta(2)m RF-reactive peptides using individual anti-epitope antibodie s. Molecular modelling studies of these peptides showed striking simil arities in three-dimensional shape among many RF-reactive peptides. Ma in-chain atoms rather than side chains seemed to contribute most direc tly to conformational similarity. Molecular simulation studies on cont rol peptides showed no conformational similarities with RF-reactive pe ptides. 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 bur simi lar main chain conformations. (C) 1997 Elsevier Science Ltd.