Autoreactive sites of human λ light chain mapped by comprehensive peptide synthesis

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Abstract
Autoantibodies reactive against immunoglobulins are associated with autoimmune disorders as well as with immunization and infection. Moreover, recent interest is focused on auto-antidiotypes because of their possible role in immunoregulation. In this study, we used a set of overlapping synthetic peptides duplicating the structure of the monoclonal human λ light chain Mcg to map autoreactive dterminants recognized by natura lantibodies present in normal polycolonal human IgG. We found that autoantibodies in human IgG react strongly with two distinct Vλ determinants corresponding to the first complementarity determining region (CDR1) and the third framework (Fr3). Antibodies showing weak reactivities against three regions of the constant domain also occur in the preparations. The antibodies directed against light chain peptides comprise less than 0.1% of the IgG pool. Analysis by direct binding and by competitive ELISA inhibition established that affinity purified antibodies specific for CDR1 and Fr3 peptide determinants react with the intact light chain Mcg as well as with the corresponding peptide. Competitive inhibition studies comparing total IgG and affinity-purified antibodies indicate that natural antibodies showing a wide range of affinities are present. The polyclonal nature of the natural antibodies is further shown by the presence of both κ and λ light chains in the purified antibodies. Although the role of such natural antibodies remains to be determined, the cross-reactivity between Vλ peptides and the intact chain suggest that they can function in regulation of antibody formation.