TY - JOUR
T1 - Functional Activity of an HIV-1 Neutralizing IgG Human Monoclonal Antibody
T2 - ADCC and Complement-Mediated Lysis
AU - Posner, Marshall R.
AU - Elboim, Hillary S.
AU - Cannon, Thomas
AU - Cavacini, Lisa
AU - Hideshima, Teru
PY - 1992/5
Y1 - 1992/5
N2 - The IgG1K, human monoclonal antibody (HMAb), F105, was studied for functional activity in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). F105 reacts with a discontinuous epitope on the CD4 binding site of the HIV-1 envelope glycoprotein, gp120, expressed on the surfaces of infected cells and neutralizes diverse viral strains at antibody concentrations readily achievable in humans. Neither F105 nor serum (diluted 1:50) from HIV seropositive donors mediate CDC against an SF2-infected cell line with rabbit or human sera as a source of complement. F105 and HIV-1 sera mediate ADCC against the SF2 strain. Normal human serum reduced spontaneous lysis of SF2 by peripheral blood monocytes (PBM). Although mixing of F105 with normal human serum reduced the lysis observed (36 ± 8 vs. 42 ± 8%), this still was significantly greater than lysis in media (30 ± 5%) or normal human serum (23 ± 6%) (p <.05). A murine antibody to CD16 significantly reduced spontaneous lysis observed with media (30 ± 5 vs. 18 ± 3%) while normal mouse serum had no effect (31 ± 7%). ADCC mediated by F105 is completely abrogated by the anti-CD16 antibody (42 ± 8 vs. 22 ± 4%), while only a fraction of ADCC mediated by HIV sera is inhibited by anti-CD16 (60 ± 9 vs. 46 ± 6%), suggesting that several populations of effector cells function in ADCC mediated by the polyclonal sera. Thus, F105, as opposed to polyclonal sera, mediates ADCC through a CD16+ PBM population.
AB - The IgG1K, human monoclonal antibody (HMAb), F105, was studied for functional activity in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). F105 reacts with a discontinuous epitope on the CD4 binding site of the HIV-1 envelope glycoprotein, gp120, expressed on the surfaces of infected cells and neutralizes diverse viral strains at antibody concentrations readily achievable in humans. Neither F105 nor serum (diluted 1:50) from HIV seropositive donors mediate CDC against an SF2-infected cell line with rabbit or human sera as a source of complement. F105 and HIV-1 sera mediate ADCC against the SF2 strain. Normal human serum reduced spontaneous lysis of SF2 by peripheral blood monocytes (PBM). Although mixing of F105 with normal human serum reduced the lysis observed (36 ± 8 vs. 42 ± 8%), this still was significantly greater than lysis in media (30 ± 5%) or normal human serum (23 ± 6%) (p <.05). A murine antibody to CD16 significantly reduced spontaneous lysis observed with media (30 ± 5 vs. 18 ± 3%) while normal mouse serum had no effect (31 ± 7%). ADCC mediated by F105 is completely abrogated by the anti-CD16 antibody (42 ± 8 vs. 22 ± 4%), while only a fraction of ADCC mediated by HIV sera is inhibited by anti-CD16 (60 ± 9 vs. 46 ± 6%), suggesting that several populations of effector cells function in ADCC mediated by the polyclonal sera. Thus, F105, as opposed to polyclonal sera, mediates ADCC through a CD16+ PBM population.
UR - http://www.scopus.com/inward/record.url?scp=0026970210&partnerID=8YFLogxK
U2 - 10.1089/aid.1992.8.553
DO - 10.1089/aid.1992.8.553
M3 - Article
C2 - 1381201
AN - SCOPUS:0026970210
SN - 0889-2229
VL - 8
SP - 553
EP - 558
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 5
ER -