Human autoantibodies to a synthetic putative T cell receptor beta-chain regulatory idiotype: expression in autoimmunity and aging.

We used synthetic peptides to analyze the human natural antibody response to V beta determinants. A major determinant recognized by IgM and IgG autoantibodies of clinically healthy individuals as well as those suffering from rheumatoid arthritis (RA) was a peptide corresponding to the first complementarity-determining region (CDR1). The natural IgM response of RA patients to this synthetic autoepitope was significantly elevated relative to that shown by healthy individuals. The levels of IgM reactivity to determinants corresponding to this region decreased with increasing age. By contrast, IgG autoantibodies to certain V beta CDR1 peptides increased markedly with age. In order to determine whether the CDR1 V beta determinant might be involved in immunization, we immunized rabbits with a human peptide that is greater than 80% identical to the homologous sequence derived from a rabbit V beta gene. As a control, the rabbits were immunized with a peptide of equal length derived from the N-terminus of the human V beta chain. Like humans, rabbits tended to have high levels of autoantibodies to the CDR1 peptide but not to the N-terminal segment. Following immunization, the rabbits produced strong IgG responses to the N-terminal peptide. By contrast, immunization with the CDR1 peptide resulted in levels of IgG antibody less than or equal to the natural activity in unimmunized rabbits. These studies indicate that the CDR1 region of Tcr V beta is a widely recognized autoantigenic portion of the Tcr that most probably functions as a regulatory epitope in man and other species.