Natural catalytic immunity is not restricted to autoantigenic substrates -Identification of a human immunodeficiency virus gp 120-cleaving antibody light chain

The autoimmune repertoire is well known from previous studies to be capable of producing catalytic antibodies directed to self-antigens. In the presen t study, we explored the ability of 26 monoclonal light chains (L chains) f rom multiple myeloma patients to cleave radiolabeled gp120, a foreign prote in. One L chain with this activity was identified. I-125-gp120 and unlabele d gp120 were cleaved at several sites by the L chain, as shown by SDS-polya crylamide gel electrophoresis, autoradiography, and immunoblotting, respect ively. The apparent dissociation constant of the L chain was 130-145 nM, in dicating high-affinity gp120 recognition. I-125-albumin was not cleaved by the L, chain, and various proteins and peptides did not inhibit gp120 cleav age by the L, chain, suggesting that the activity is not a nonspecific phen omenon. The substrate recognition determinants maybe conserved in different HIV-1 strains, because gp120 isolated from strains SF2, MN, and IIIB was f ound to be cleaved by the L, chain. Micromolar concentrations of a syntheti c peptide corresponding to residues 23-30 of gp120 inhibited the cleavage o f 125I-gp120, suggesting that these residues are components of the epitope recognized by the L, chain. The toxic effect of gp120 in neuronal cultures was reduced by about 100-fold by pretreatment of the protein with the L cha in. These observations open the possibility of utilizing gp120-cleaving ant ibodies in the treatment of AIDS.