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

Appl Biochem Biotechnol. 2000 Jan-Mar;83(1-3):71-82; discussion 82-4, 145-53. doi: 10.1385/abab:83:1-3:71.

Abstract

The autoimmune repertoire is well known from previous studies to be capable of producing catalytic antibodies directed to self-antigens. In the present study, we explored the ability of 26 monoclonal light chains (L chains) from multiple myeloma patients to cleave radiolabeled gp120, a foreign protein. One L chain with this activity was identified. 125I-gp120 and unlabeled gp120 were cleaved at several sites by the L chain, as shown by SDS-polyacrylamide gel electrophoresis, autoradiography, and immunoblotting, respectively. The apparent dissociation constant of the L chain was 130-145 nM, indicating high-affinity gp120 recognition. 125I-albumin was not cleaved by the L chain, and various proteins and peptides did not inhibit gp120 cleavage by the L chain, suggesting that the activity is not a nonspecific phenomenon. The substrate recognition determinants may be conserved in different HIV-1 strains, because gp120 isolated from strains SF2, MN, and IIIB was found to be cleaved by the L chain. Micromolar concentrations of a synthetic peptide corresponding to residues 23-30 of gp120 inhibited the cleavage of 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 chain. These observations open the possibility of utilizing gp120-cleaving antibodies in the treatment of AIDS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Catalytic / metabolism*
  • Antibodies, Monoclonal / metabolism
  • Antibody Affinity
  • Antibody Specificity
  • Autoantibodies / metabolism
  • Autoantigens / metabolism
  • CHO Cells
  • Cells, Cultured
  • Cricetinae
  • HIV Antibodies / metabolism
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / toxicity
  • Humans
  • Immunity, Innate*
  • Immunoglobulin Light Chains / metabolism
  • In Vitro Techniques
  • Multiple Myeloma / immunology
  • Neurons / drug effects
  • Rats

Substances

  • Antibodies, Catalytic
  • Antibodies, Monoclonal
  • Autoantibodies
  • Autoantigens
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin Light Chains