A human anti-HIV autoantibody enhances EBV transformation and HIV infection.
A highly specific, human IgG mAb, F223, which reacts with both HIV-1-infected cells and uninfected lymphoid cells, has been derived. F223 reacts with gp120 but fails to neutralize viral infection. The antibody does enhance HIV-1 infection in a complement-dependent manner. The autoantigen recognized by F223 is expressed on a small percentage of T cells and NK cells and the majority of B cells. Immunoprecipitation demonstrates F223 reactivity with an as of yet unidentified 159-kDa protein in uninfected lymphoid cells. This reactivity with uninfected cells is inhibited by free gp120 demonstrating the cross-reactive nature of this antibody. The F223 light chain demonstrates strong homology to VLlambda2 family genes whereas the heavy chain is most homologous (84%) to the germline gene VH3-H.11. In vivo usage of VH3 family genes by F223 and an anti-HIV-1 (gp41) human mAb, 3D6, with related autoreactivity, suggests that VH3 sequences may be important components of potentially pathogenic human anti-HIV-1 envelope autoantibodies. F223 was isolated from an HIV-1 infected individual with lymphoma and in vitro F223 significantly enhances EBV transformation of normal B cells and increases immunoglobulin production without affecting B cell proliferation. Characterization of this antibody response may provide important insights and mechanistic information on HIV pathogenesis.
Cavacini
L A
LA
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Wisnewski
A
A
Peterson
J E
JE
Montefiori
D
D
Emes
C
C
Duval
M
M
Kingsbury
G
G
Wang
A
A
Scadden
D
D
Posner
M R
MR
D019138:Antibodies, Blocking / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D002460:Cell Line; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011233:Precipitin Tests; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014170:Transformation, Genetic / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015483:HIV Antibodies