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I F Luescher

Publications and source records attributed to I F Luescher.

40 records · Page 3Linked to original sources
PubMed1990

Phospholipids enhance the binding of peptides to class II major histocompatibility molecules.

The binding of a lysozyme and ovalbumin peptide to purified class II major histocompatibility molecules in detergents was increased by the addition of certain lipids. Natural lipids from B lymphoma cells enhanced the binding and so did phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Phosphatidylethanolamine, sphingomyelin, and cholesterol had no effect. There was no major difference between the effects of a phospholipid and its lyso derivative. As studied with phosphatidylcholine, the increase in peptide binding was also dependent on the fatty acid composition of the lipid. The binding affinity was increased 10- to 50-fold in the presence of lipid as a result of an increase in the association rate while the off-rate remained essentially unchanged. Our results suggest that lipids, directly or indirectly, induce conformational changes in class II molecules that favor their peptide-binding property.

Amino Acid Sequence↗
PubMed1988

Macrophages pulsed with sterol-conjugated benzylpenicilloylated eicosa-lysine induce T cell-mediated suppression of IgE antibody formation in mice.

The conjugation of two lipophilic p-oxymethylbenzyl-3 beta-cholestanylsuccinate groups to fully benzylpenicilloylated eicosa-L-lysine [BPO20Lys20(OSuco)2] greatly potentiated its ability to suppress anti-BPO IgE antibody formation in vivo in mice. This enhanced tolerogenicity was due to the ability of BPO20Lys20(OSuco)2 to induce T suppressor cells (Luescher, I.F. et al., Eur. J. Immunol. 1984. 14: 68). In the present study the role of adherent cells in the induction of T suppressor cells by BPO20Lys20(OSuco)2 was investigated. Low numbers of macrophages pulsed in vitro with BPO20Lys20(OSuco)2, but not with the hydrophilic analog BPO21Lys20-OH, suppressed anti-BPO IgE antibody formation upon transfer into syngeneic recipients. This suppression was antigen and IgE specific, and was manifested in naive as well as in previously immunized mice. By cell transfer experiments it was found that the suppression was sensitive to cyclophosphamide. The IgE suppression was not due to carry-over of BPO20Lys20(OSuco)2 by the transferred macrophages since the amount of cell-associated antigen was approximately 500-fold too low to account for the observed suppressions. The capability of BPO20Lys20(OSuco)2 to elicit anaphylaxis in passively sensitized rats was significantly lower in comparison to the hydrophilic analog BPO21Lys20-OH. Adherent cells pulsed with BPO20Lys20(OSuco)2, although strongly suppressing IgE antibody formation, failed to elicit any detectable anaphylaxis. The role of adherent cells in the induction of T cell-mediated suppression of IgE antibody formation by lipid-modified antigens is discussed and novel therapeutical concepts to achieve desensitization of drug allergic individuals are suggested.

Animals↗
PubMed1988

Binding of photoreactive lysozyme peptides to murine histocompatibility class II molecules.

We have studied the interaction of six photoreactive conjugates of the immunogenic hen egg-white lysozyme peptides HEL(46-61) or HEL(49-61) with the murine histocompatibility class II molecules I-Ak, I-Ad, I-Ek, and I-Ed. All compounds tested selectively labeled the alpha chain of the class II molecules. This was true when testing class II molecules on cell membranes or solubilized in detergents. The COOH-terminal conjugate of HEL(49-61) with (4-azidobenzoyl)cystine preferentially labeled I-Ak. However, addition of hydroxyl or iodine substituents to the photoreactive moiety increased the labeling efficiency and resulted in labeling of the other class II molecules. The data suggest that the photoreactive groups enhanced the binding affinities of these peptides to class II molecules, reflected by the increased labeling efficiencies. Conversely, introduction of an iodine substitution into the tyrosine residue of HEL(46-61) or HEL(49-61) strongly decreased the photoaffinity labeling, possibly due to steric interference with ligand binding to class II molecules. Judicious use of photoaffinity probes that conserve binding specificity of the peptide should be useful for mapping the antigen-binding site of a class II molecule.

Affinity Labels↗