Efficacy of HIV-specific and 'antibody-independent' mechanisms for complement activation by HIV-infected cells.
Previous studies in this laboratory have shown that efficient activation of complement (C) on HIV isolates and HIV-infected cells requires the binding of specific anti-HIV antibodies, while other investigators have observed 'antibody-independent' C activation. In an attempt to clarify these disparate findings, we investigated the effect of several variables on C activation by HIV-infected cells using flow cytometric analysis of C3 deposition. Antibody-mediated C activation using pooled sera from infected persons or human MoAbs directed against the V3 region of gp120 was always substantially higher than activation without antibody. Normal human serum (NHS) from a subset of HIV antibody-negative donors did, however, induce low levels of C3 deposition. Differences in C3 activation between the various NHS did not correlate with total haemolytic C levels or mannose-binding protein (MBP) levels. IgM isolated from NHS that induced high levels of C activation was at least partly responsible for the 'antibody-independent' C activation. Although there appeared to be a correlation between NHS that induced C activation and the presence of anti-blood type B IgM, absorption of anti-B did not abrogate the C3 deposition. Additionally, MoAb to the B antigen did not induce C3 deposition. These studies show that IgM in sera from HIV-uninfected donors can induce C3 deposition on HIV-infected cells, but that specific antibody-dependent C activation is substantially more efficient. Therefore, 'antibody-independent' C activation on HIV-infected cells may, in some cases, be more accurately described as HIV-cross-reactive antibody-dependent C activation.
Department of Immunology/Microbiology, Rush Medical School, Chicago, IL 60612.
M N
MN
Saarloos
T F
TF
Lint
G T
GT
Spear
D000017:ABO Blood-Group System / Q000276:immunology; D000918:Antibody Specificity; D002460:Cell Line; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology; D015941:Complement Hemolytic Activity Assay / Q000379:methods; D003429:Cross Reactions / Q000276:immunology; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology
D000017:ABO Blood-Group System; D003176:Complement C3; D015483:HIV Antibodies; D007075:Immunoglobulin M