Human lipooligosaccharide IGG that prevents endemic meningococcal disease recognizes an internal lacto-N-neotetraose structure.
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 (nLc4) LOS α chain. We used a set of mutants that have successive saccharide deletions from the nLc4 α chain to characterize further the binding and bactericidal activity of nLc4 LOS IgG. We found that the nLc4 α chain conforms at least four different antigens. We separately purified IgG that required the nLc4 (non-reducing) terminal galactose (Gal) for binding and IgG that bound the truncated nLc3 α chain that lacks this Gal residue. IgG that bound the internal nLc3 α chain killed both L3,7 and L2,4 strains, whereas IgG that required the nLc4 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 nLc4 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.
Department of Veterans Affairs Medical Center, San Francisco, California 94121.
Hui
H
Cheng
Department of Veterans Affairs Medical Center, San Francisco, California 94121.
Zhijie
Z
Yang
Department of Veterans Affairs Medical Center, San Francisco, California 94121; Department of Pediatrics, University of California, San Francisco, California 94121.
Michele M
MM
Estabrook
Department of Veterans Affairs Medical Center, San Francisco, California 94121.
Constance M
CM
John
Department of Veterans Affairs Medical Center, San Francisco, California 94121; Department of Laboratory Medicine, University of California, San Francisco, California 94121.
Gary A
GA
Jarvis
Department of Veterans Affairs Medical Center, San Francisco, California 94121.
Stephanie
S
McLaughlin
Department of Veterans Affairs Medical Center, San Francisco, California 94121; Department of Laboratory Medicine, University of California, San Francisco, California 94121. Electronic address: crapaud@loursage.org.
J McLeod
JM
Griffiss
D000941:Antigens / Q000737:chemistry; D002240:Carbohydrate Sequence; D003141:Communicable Diseases / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods; D022401:Meningococcal Vaccines / Q000276:immunology; D009154:Mutation; D009345:Neisseria meningitidis / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry*
D000941:Antigens; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D022401:Meningococcal Vaccines; D009841:Oligonucleotides; D009844:Oligosaccharides; C023023:lipid-linked oligosaccharides; C013084:lacto-N-neotetraose