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 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.
Paul
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Department of Pathology, University of Texas Medical School, Houston 77030, USA.
Kalaga
R S
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Gololobov
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Brenneman
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D
D000818:Animals; D017151:Antibodies, Catalytic / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000915:Antibody Affinity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D015483:HIV Antibodies / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000633:toxicity; D006801:Humans; D007113:Immunity, Innate; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D066298:In Vitro Techniques; D009101:Multiple Myeloma / Q000276:immunology; D009474:Neurons / Q000187:drug effects; D051381:Rats
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007147:Immunoglobulin Light Chains