Identification of an idiotypic peptide recognized by autoantibodies in human immunodeficiency virus-1-infected individuals.
Antibodies against HIV-1 proteins in HIV-1-infected individuals share a cross-reactive idiotype defined by the monoclonal antiidiotypic antibody 1F7 (5). Using a computer algorithm based on the molecular recognition theory, regions of inverse hydropathy between the variable sequence of 1F7 and human monoclonal anti-HIV-1 antibodies were identified, which are assumed to be involved in idiotype-antiidiotype contacts. A peptide was designed from the proposed contact in the variable heavy chain framework 3-complementarity determining region 3 (FR3-CDR3) of human antibodies and was synthesized. This peptide is recognized by the antiidiotype 1F7 and inhibits the binding of 1F7 to human anti-HIV-1 antibodies which express the 1F7 idiotype. A survey of normal and HIV-1-infected sera revealed the presence of antibodies in infected sera which bind to the FR3-CDR3 peptide. The biological relevance of autoantibodies against a self idiotope associated with HIV-1 infection is discussed in the context of the regulation of the antibody response to HIV-1.
Wang
Q L
QL
Markey Cancer Center, University of Kentucky Medical Center, Lexington 40536-0096, USA.
Wang
H T
HT
Blalock
E
E
Müller
S
S
Köhler
H
H
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D003198:Computer Simulation; D003429:Cross Reactions; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000737:chemistry / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D001324:Autoantigens; D015483:HIV Antibodies; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments