The solution supramolecular structure of α2 → 8 polysialic acid suggests a structural cause for its low immunogenicity.

Abstract

α2 → 8 polysialic acid (polySia), the capsular polysaccharide on Neisseria meningitidis serogroup B and Escherichia coli K1, elicits poor immunogenic properties. A solution structure might clarify the cause. From X-ray and neutron small-angle scattering, we find that the solution supramolecular structure of polySia exhibits parallel-chain binding. Also, striking structural changes occur upon the addition of calcium to these solutions but still with the parallel motif. The major histocompatibility complex requires entities in the molecular weight range of 600-3000 Da, but the solution structures determined here argue that in endosomes polySia oligomers of the correct size to be immunologically effective are instead bound up as parallel chains. This is expected to reduce the possible concentrations of the effective oligomers and so reduce the immunogenic capability of α2 → 8 polysialic acid.