Two Distinct Antigenic Types of the Polysaccharide Chains of Helicobacter pylori Lipopolysaccharides Characterized by Reactivity with Sera from Humans with Natural Infection

Abstract

We have purified lipopolysaccharides (LPS) from 10 Helicobacter pylori clinical isolates which were selected on the basis of chemotype and antigenic variation. Data from immunoblotting of the purified LPS with sera from humans with H. pylori infection and from absorption of the sera with LPS indicated the presence of two distinct epitopes, termed the highly antigenic and the weakly antigenic epitopes, on the polysaccharide chains. Among 68 H. pylori clinical isolates, all smooth strains possessed either epitope; the epitopes were each carried by about 50% of the smooth strains. Thus, H. pylori strains can be classified into three types on the basis of their antigenicity in humans: those with smooth LPS carrying the highly antigenic epitope, those with smooth LPS carrying the weakly antigenic epitope, and those with rough LPS. Sera from humans with H. pylori infection could be grouped into three categories: those containing immunoglobulin G (IgG) antibodies against the highly antigenic epitope, those containing IgG against the weakly antigenic epitope, and those containing both specific IgGs; these groups made up about 50%, less than 10%, and about 40%, respectively, of all infected sera tested. In other words, IgG against the highly antigenic epitope were detected in more than 90% of H. pylori-infected individuals with high titers. IgG against the weakly antigenic epitope were detected in about 50% of the sera tested; however, the antibody titers were low. The two human epitopes existed independently from the mimic structures of Lewis antigens, which are known to be an important epitope of H. pylori LPS. No significant relationship between the reactivities toward purified LPS of human sera and a panel of anti-Lewis antigen antibodies was found. Moreover, the reactivities of the anti-Lewis antigen antibodies, but not human sera, were sensitive to particular ␣-L-fucosidases. The human epitopes appeared to be located on O-polysaccharide chains containing endo-␤-galactosidase-sensitive galactose residues as the backbone. Data from chemical analyses indicated that all LPS commonly contained galactose, glucosamine, glucose, and fucose (except one rough strain) as probable polysaccharide components, together with typical components of inner core and lipid A. We were not able to distinguish between the differences of antigenicity in humans by on the basis of the chemical composition of the LPS.

Phenotypic Variation ofHelicobacter pyloriIsolates from Geographically Distinct Regions Detected by Lectin Typing

“…These phenotypic variations of H. pylori which coincide with differences in human populations would argue for the presence of host-adapted strains (6). (1,8,17,26,35,36), although some isolates remain untypeable with anti-Le antibodies (8,11,26,32). Importantly, the present lectin typing system has detected greater diversity among isolates than has been detectable with anti-Le antibodies (26) and has highlighted geographical differences in carbohydrate expression by H. pylori isolates due to its capacity for broader recognition of variations in carbohydrate structures (10).…”

Helicobacter pylori with a Truncated Lipopolysaccharide O Chain Fails To Induce Gastritis in SCID Mice Injected with Splenocytes from Wild-Type C57BL/6J Mice

“…Overexpression of anti-Lewis antibodies in mice has been associated with development of gastritis (5), suggesting a direct role for antibodies in disease. Finally, H. pylori O antigens that do not mimic Lewis antigens have been reported (1,26,37,58), and serological response to non-Lewis O antigens has been associated with clinical disease (57).…”

“…In addition to Lewis antigens, H. pylori expresses other O-chain antigens that may also be predictive of disease. For example, Yokota et al have identified several O antigens that appear to correlate with disease as do the Lewis epitopes (57,58). In a study by Logan et al (29), an H. pylori mutant expressing truncated LPS failed to induce a serological response in mice, indicating low immunogenicity and potentially a role in pathogenesis, at least in mice.…”

Helicobacter pylori Lipopolysaccharide as a Possible Pathogenic Factor for Gastric Carcinogenesis

“…Strains having the highly-antigenic epitope-carrying LPS are frequently found in those derived from patients with chronic gastritis. Strains having the weakly-antigenic epitopecarrying LPS are predominantly found in those derived from patients with gastric cancer (Yokota et al, 2000b;Yokota et al, 1997) (Fig. 4).…”

“…The reactivity of human antisera to H. pylori LPS derived from various strains was examined and a classification of H. pylori LPS has been proposed based on the antigenicity of O-polysaccharides to humans, namely highly-antigenic-epitope-carrying LPS and weakly-antigenic-epitope-carrying LPS Yokota et al, 2000b). The two epitopes were clearly characterized by examining serum absorption by LPS (Fig.…”