Structural characteristics influencing the carrier function of synthetic branched polypeptides based on poly[Lys-(DL-Ala)3)]backbone.
Effective carrier function of selected representatives of new branched polypeptides covalently coupled with the synthetic monovalent hapten, oxazolone was studied. The effectiveness of oxazolone-synthetic polypeptide conjugates in inducing oxazolone-as well as carrier-specific antibody responses in inbred mice was compared to that of bovine serum albumin (BSA)- and KLH-oxazolone conjugates. The synthetic polypeptides, poly[Lys-(D-Leui-DL-Alam)] (D-LAK), LAK and FAK, as well as the common poly[Lys-(DL-Alam)](AK) core covalently coupled to oxazolone (Ox) induced a T cell-dependent antibody response when repeatedly administered with or without Freund's adjuvant in mice. This was evidenced by: the increasing titer of oxazolone-specific IgG during the course of the memory response; the appearance of all IgG subclasses; the effective oxazolone-specific priming by the conjugates; and the induction of an intense oxazolone- and carrier-specific DTH reaction. Although the oxazolone-specific antibody response was 10-100 times lower than that induced by KLH- or BSA-oxazolone conjugates, it was accompanied by a lower level or no detectable carrier-specific antibody response despite an effective carrier-specific T cell-mediated response. Significant differences were observed between the effectiveness of synthetic polypeptides used as carrier: highest oxazolone-specific antibody titers were observed using the AK, LAK and FAK conjugates. The intensity and specificity of the DTH reaction and antibody response induced by the carrier-oxazolone conjugates suggested that the distinct effectiveness of L- and D-amino acid-containing conjugates (LAK vs D-LAK and FAK vs D-FAK) was dependent on altered B cell recognition of the haptenic group. Circular dichroism (CD) spectra indicating different local orientation of oxazolone, when coupled to L or D side chain-terminating amino acids, support this suggestion.
Rajnavölgyi
E
E
Department of Immunology, L. Eötvös University, Göd, Hungary.
Lányi
A
A
Hudecz
F
F
Kurucz
I
I
Kiss
K
K
László
G
G
Szekerke
M
M
Gergely
J
J
D000596:Amino Acids / Q000276:immunology; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010081:Oxazolone / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002352:Carrier Proteins; D007074:Immunoglobulin G; D010455:Peptides; D010081:Oxazolone