Membrane-controlled depletion of complement activity by spin-label-specific IgM

Abstract

Complement depletion mediated by high molecular weight (IgM) rabbit antibodies specifically bound to spin-label lipid haptens dispersed in model membranes is controlled by various physical attributes of those membranes other than the total number of exposed determinants that they provide. Carrier lipids used at 320 were (i) a "fluid" phosphatidylcholine (PC), (if) a "solid" PC, and (iil) a cholesterol/PC mixture.The concentration of hapten in the plane of the membranes (two-dimensional concentration) was varied while the overall hapten molarity (three-dimensional concentration) was kept constant.Both specific binding and the efficiency of depletion by IgM are markedly enhanced by systematically decreasing the average distance between haptens (co -_ 26 A). Heterogeneous distribution was found to be more favorable than a random homogeneous distribution of the same number of haptens in the same total quantity of lipids. IgM efficiency is also markedly increased by the inclusion of cholesterol in PC membranes, an effect thought to result from enhanced projection of the determinant from the surface of the membrane and hence increased accessibility to the antibody-binding site. Furthermore, the efficiency of IgM was increased by using haptens dispersed in fluid rather than in solid PC membranes.The results are consistent with the hypothesis that IgM molecules must be bound to a critical multiple of antigenic determinants at a membrane surface in order to induce complement-mediated attack and that subtle variation of the physical state of membrane antigens can be the crucial factor in determining the outcome of this type of efferent immune response.The relative cytotoxic efficiencies of different effector components of the immune system against the same target membrane can differ by several orders of magnitude. For example, erythrocyte cytolysis by antibody-dependent monocytes is typically about 103 times more efficient per IgG antibody molecule than is cytolysis of the same cells with the same antibody in the presence of complement (C) (1, 2). Likewise, specific antierythrocyte antibodies of the IgM class are about 103 times more efficient in C-mediated lysis than are specific IgG antibodies (3, 4). On the other hand, efficiencies of the same effector components against different target membranes can differ widely (5-10). In attempting to elucidate mechanistic differences in molecular terms, we have turned to the use of model membranes (liposomes or vesicles) to serve as targets for these various components of the immune system (7-12). Because the physical and chemical properties of such target membranes can be varied, we can hope to discern which special characteristics of an immune response are directly related to properties of components of the immune system and whichThe costs of publication of this article were defrayed in part by the payment of page charges from funds made available to support the research which is the subject of the article. This article must therefore be hereby marked "advertisement" in...

Dynamic properties of the haptenic site of lipid haptens in phosphatidylcholine membranes. Their relation to the phase transition of the host lattice

“…The spectra of spin-label lipid haptens in membranes were rather anisotropic, and the low field peak was the narrowest of the three sharp lines. This characteristic coincided with the results obtained by Smith's group (Hsia et al, 1970;Schreier-Muccillo et al, 1973) using the stearamide spin-label and by McConnell's group (Bruilet et al, 1977;Brfulet and McConnell, 1977;Humphries and McConnell, 1977;Humphries, 1980) using the same spinlabel as us. According to Griffith and Jost (1976), axial rotation about the x-axis should result in the spectrum with the narrowest low field peak, while rotation about the other axes lead to the central peak being the narrowest.…”

Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells

“…However, it is possible that the accessibility of anti-KMP-11 Abs may be due to the rigidity of the membrane, as shown by other workers with model membranes (26). An alternative possibility is that because of its ability to fold and unfold KMP-11 may interact with the membrane lipid (18).…”

Antibody interaction with a membrane-bound fluorescent ligand on synthetic lipid vesicles

“…Previous studies on the interaction of IgG antibody specific for 2,4-dinitrophenyl (Dnp) or paramagnetic nitroxide (spinlabel) ligands which were attached to a phosopholipid in the liposomal membrane indicated that a spacer between the phospholipid head group and the antigenic determinant facilitated the binding of specific antibody (Six et al, 1973(Six et al, , 1974; Brület & McConnell, 1976Humphries & McConnell, 1977). We, therefore, synthesized a probe which incorporated lysine as a spacer in order to separate the phospholipid head group and the haptenic group by 10-12 Á.…”