Expression of histo-blood group antigens by lipopolysaccharides of Helicobacter pylori strains from Asian hosts: the propensity to express type 1 blood-group antigens

Mucins isolated from the stomach of Rhesus monkey are oligomeric glycoproteins with a similar mass, density, glycoform profile and tissue localization as human MUC5AC and MUC6. Antibodies raised against the human mucins recognize those from monkey, which thus appear to be orthologous to those from human beings. Rhesus monkey muc5ac and muc6 are produced by the gastric-surface epithelium and glands respectively, and occur as three distinct glycoforms. The mucins are substituted with the histo blood-group antigens B, Lea (Lewis a), Leb, Lex, Ley, H-type-2, the Tn-antigen, the T-antigen, the sialyl-Lex and sialyl-Lea structures, and the expression of these determinants varies between individuals. At neutral pH, Helicobacter pylori strains expressing BabA (blood-group antigen-binding adhesin) bind Rhesus monkey gastric mucins via the Leb or H-type-1 structures, apparently on muc5ac, as well as on a smaller putative mucin, and binding is inhibited by Leb or H-type-1 conjugates. A SabA (sialic acid-binding adhesin)-positive H. pylori mutant binds to sialyl-Lex-positive mucins to a smaller extent compared with the BabA-positive strains. At acidic pH, the microbe binds to mucins substituted by sialylated structures such as sialyl-Lex and sialylated type-2 core, and this binding is inhibited by DNA and dextran sulphate. Thus mucin–H. pylori binding occurs via at least three different mechanisms: (1) BabA-dependent binding to Leb and related structures, (2) SabA-dependent binding to sialyl-Lex and (3) binding through a charge-mediated mechanism to sialylated structures at low pH values.

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Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity.

Infection and Immunity ◽

10.1128/iai.64.6.2031-2040.1996 ◽

1996 ◽

Vol 64 (6) ◽

pp. 2031-2040 ◽

Cited By ~ 266

Author(s):

B J Appelmelk ◽

I Simoons-Smit ◽

R Negrini ◽

A P Moran ◽

G O Aspinall ◽

...

Keyword(s):

Helicobacter Pylori ◽

Blood Group ◽

Potential Role ◽

Molecular Mimicry ◽

Blood Group Antigens ◽

Lewis Blood Group

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Role of Lewis A and Lewis B Blood Group Antigens in Helicobacter pylori Infection

Helicobacter ◽

10.1111/j.1083-4389.2004.00236.x ◽

2004 ◽

Vol 9 (4) ◽

pp. 324-329 ◽

Cited By ~ 7

Author(s):

Dietrich Rothenbacher ◽

Maria Weyermann ◽

Gunter Bode ◽

Murrat Kulaksiz ◽

Bernd Stahl ◽

...

Keyword(s):

Helicobacter Pylori ◽

Blood Group ◽

Helicobacter Pylori Infection ◽

Blood Group Antigens ◽

B Blood Group ◽

Lewis A

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Association of Type 1 Blood Group Antigens with Urinary Tract Infections in Children with Genitourinary Structural Abnormalities

The Journal of Urology ◽

10.1016/s0022-5347(17)39492-2 ◽

1990 ◽

Vol 144 (2 Part 2) ◽

pp. 469-473 ◽

Cited By ~ 4

Author(s):

Joel Sheinfeld ◽

Carlos Cordon-Cardo ◽

William R. Fair ◽

David D. Wartinger ◽

Ronald Rabinowitz

Keyword(s):

Urinary Tract ◽

Blood Group ◽

Urinary Tract Infections ◽

Blood Group Antigens ◽

Structural Abnormalities ◽

Tract Infections

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Histo-blood group antigens: a common niche for norovirus and rotavirus

Expert Reviews in Molecular Medicine ◽

10.1017/erm.2014.2 ◽

2014 ◽

Vol 16 ◽

Cited By ~ 93

Author(s):

Ming Tan ◽

Xi Jiang

Keyword(s):

Helicobacter Pylori ◽

Structural Analysis ◽

Blood Group ◽

Bacterial Pathogen ◽

Binding Pocket ◽

Lewis Antigens ◽

Blood Group Antigens ◽

Exploratory Research ◽

Binding Interfaces ◽

Selection Of

Noroviruses (NoVs) and rotaviruses (RVs), the two most important causes of viral acute gastroenteritis, are found to recognise histo-blood group antigens (HBGAs) as receptors or ligands for attachment. Human HBGAs are highly polymorphic containing ABO, secretor and Lewis antigens. In addition, both NoVs and RVs are highly diverse in how they recognise these HBGAs. Structural analysis of the HBGA-binding interfaces of NoVs revealed a conserved central binding pocket (CBP) interacting with a common major binding saccharide (MaBS) of HBGAs and a variable surrounding region interacting with additional minor binding saccharides. The conserved CBP indicates a strong selection of NoVs by the host HBGAs, whereas the variable surrounding region explains the diverse recognition patterns of different HBGAs by NoVs and RVs as functional adaptations of the viruses to human HBGAs. Diverse recognition of HBGAs has also been found in bacterial pathogenHelicobacter pylori. Thus, exploratory research into whether such diverse recognitions also occur for other viral and bacterial pathogens that recognise HBGAs is warranted.

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Characterization of murine monoclonal antibodies againstHelicobacter pylorilipopolysaccharide specific for Lexand Leyblood group determinants

Biochemistry and Cell Biology ◽

10.1139/o05-052 ◽

2005 ◽

Vol 83 (5) ◽

pp. 589-596 ◽

Cited By ~ 11

Author(s):

Eleonora Altman ◽

Blair A Harrison ◽

Tomoko Hirama ◽

Vandana Chandan ◽

Rebecca To ◽

...

Keyword(s):

Helicobacter Pylori ◽

Monoclonal Antibodies ◽

Blood Group ◽

Cell Envelope ◽

Mucosal Cell ◽

Blood Group Antigens ◽

Binding Characteristics ◽

Igg3 Subclass ◽

H Pylori

The cell envelope of Helicobacter pylori contains lipopolysaccharide (LPS), the O-chain of which expresses type 2 Lexand Leyblood group antigens, which mimic human gastric mucosal cell-surface glycoconjugates and may contribute to the survival of H. pylori in gastric mucosa. Here we describe the generation of monoclonal antibodies specific for Lexand Leyblood group determinants and the characterization of their binding properties using purified, structurally defined H. pylori LPS, synthetic glycoconjugates, and H. pylori cells. Analysis of oligosaccharide binding by SPR provided a rapid and reliable means for characterization of antibody affinities. One of the antibodies, anti-Lex, was of IgG3 subclass and had superior binding characteristics as compared with the commercially available anti-LexIgM. These antibodies could have potential in the immunodiagnosis of certain types of cancer, in serotyping of H. pylori isolates, and in structure–function studies.Key words: Helicobacter pylori, lipopolysaccharide, monoclonal antibodies, Lewis determinants, immunodiagnosis.

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The Distribution of Type 1 Chain ABH and Related Histo-Blood Group Antigens in Normal Cycling Human Endometrium

International Journal of Gynecological Pathology ◽

10.1097/00004347-199301000-00010 ◽

1993 ◽

Vol 12 (1) ◽

pp. 70-79 ◽

Cited By ~ 18

Author(s):

Vibeke Ravn ◽

Christence Stubbe Teglbjaerg ◽

Ulla Mandel ◽

Erik Dabelsteen

Keyword(s):

Blood Group ◽

Human Endometrium ◽

Blood Group Antigens

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Molecular basis of P[6] and P[8] major human rotavirus VP8* domain interactions with histo-blood group antigens

10.1101/512301 ◽

2019 ◽

Cited By ~ 2

Author(s):

Shenyuan Xu ◽

Yang Liu ◽

Ming Tan ◽

Weiming Zhong ◽

Dandan Zhao ◽

...

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Blood Group ◽

Molecular Basis ◽

Disease Burden ◽

Binding Domain ◽

Specific Cell ◽

Blood Group Antigens ◽

Nuclear Magnetic

AbstractInitial cell attachment of rotavirus (RV) to specific cell surface glycans, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as ligands or receptors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b and H type 1 antigens, while P[6], which is one of the other genotypes in P[II], only recognizes the H type 1 antigen. The molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leb and type 1 HBGAs and for P[6] recognition of H type 1 HBGAs. Unlike P[6] VP8* that recognizes H type 1 HGBAs in a binding surface composed of an α-helix and a β-sheet, referred as “βα binding domain”, the P[8] VP8* binds the type 1 HBGAs requiring the presence of the Lewis epitope in a previously undescribed pocket formed by two β-sheets, referred as “ββ binding domain”. The observation that P[6] and P[8] VP8* domains recognize different glycan structures at distinct binding sites supports the hypothesis that RV evolution is driven, at least in part, by selective pressure driven adaptation to HBGA structural diversity of their natural hosts living in the world. Recognition of the role that HBGAs play in driving RV evolution is essential to understanding RV diversity, host ranges, disease burden and zoonosis and to developing strategies to improve vaccines against RV infections.Author summaryRotaviruses (RV)s are the main cause of severe diarrhea in humans and animals. Significant advances in understanding RV diversity, evolution and epidemiology have been made after discovering that RVs recognize histo-blood group antigens (HBGAs) as host cell receptors. While different RV strains are known to have distinct binding preferences for HBGA receptors, the molecular basis in controlling strain-specific host ranges remains unclear. In this study, we used solution nuclear magnetic resonance to determine the molecular level details for interactions of the human P[8] and P[6] RV VP8* domains with their HBGA receptors. The distinct binding patterns observed between these major human RVs and their respective receptor ligands provides insight into the evolutionary relationships between different P[II] genotypes that ultimately determine host ranges, disease burden, zoonosis and epidemiology, which may impact future strategies for vaccine development against RVs.

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