AUTOREACTIVE SITES OF HUMAN LAMBDA-LIGHT CHAIN MAPPED BY COMPREHENSIVE PEPTIDE-SYNTHESIS

Autoantibodies reactive against immunoglobulins are associated with au toimmune disorders as well as with immunization and infection. Moreove r, recent interest is focused on auto-antidiotypes because of their po ssible role in immunoregulation. In this study, we used a set of overl apping synthetic peptides duplicating the structure of the monoclonal human lambda light chain Meg to map autoreactive dterminants recognize d by natural antibodies present in normal polycolonal human IgG. We fo und that autoantibodies in human IgG react strongly with two distinct V lambda determinants corresponding to the first complementarity deter mining region (CDR1) and the third framework (Fr3). Antibodies showing weak reactivities against three regions of the constant domain also o ccur in the preparations. The antibodies directed against light chain peptides comprise less than 0.1% of the IgG pool. Analysis by direct b inding and by competitive ELISA inhibition established that affinity p urified antibodies specific for CDR1 and Fr3 peptide determinants reac t with the intact light chain Meg as well as with the corresponding pe ptide. Competitive inhibition studies comparing total IgG and affinity -purified antibodies indicate that natural antibodies showing a wide r ange of affinities are present. The polyclonal nature of the natural a ntibodies is further shown by the presence of both kappa and lambda li ght chains in the purified antibodies. Although the role of such natur al antibodies remains to be determined, the cross-reactivity between V lambda peptides and the intact chain suggest that they can function i n regulation of antibody formation.