Human lipooligosaccharide IGG that prevents endemic meningococcal disease recognizes an internal lacto-N-neotetraose structure

Hui Cheng, Zhijie Yang, Michele M. Estabrook, Constance M. John, Gary A. Jarvis, Stephanie McLaughlin, J. McLeod Griffiss

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Antibodies that initiate complement-mediated killing of Neisseria meningitidis as they enter the bloodstream from the oropharynx protect against disseminated disease. Human IgGs that bind the neisserial L7 lipooligosaccharide (LOS) are bactericidal for L3,7 and L2,4 meningococci in the presence of human complement. These strains share a lacto-N-neotetraose (nLc 4) LOS α chain. We used a set of mutants that have successive saccharide deletions from the nLc 4 α chain to characterize further the binding and bactericidal activity of nLc 4 LOS IgG. We found that the nLc 4 α chain conforms at least four different antigens. We separately purified IgG that required the nLc 4(non-reducing) terminal galactose (Gal) for binding and IgG that bound the truncated nLc 3 α chain that lacks this Gal residue. IgG that bound the internal nLc 3 α chain killed both L3,7 and L2,4 strains, whereas IgG that required the nLc 4 terminal Gal residue for binding killed L2,4 stains but not L3,7 strains. These results show that the diversity of LOS antibodies in human serum is as much a function of the conformation of multiple antigens by a single glycoform as of the production of multiple glycoforms. Differences in sensitivity to killing by human nLc 4 LOS IgG may account for the fact that fully two-thirds of endemic group B meningococcal disease in infants and children is caused by L3,7 strains, but only 20% is caused by L2,4 stains.

Original languageEnglish
Pages (from-to)43622-43633
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number51
DOIs
StatePublished - Dec 23 2011
Externally publishedYes

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