Lipopolysaccharide Lewis Antigens

As determined by serological techniques, the O-antigen of lipopolysaccharide (LPS) of more than 80% of Helicobacter pylori strains tested worldwide express Lewis blood group antigens (36, 60, 71). This percentage possibly represents an underestimation; it was demonstrated that some H. pylori strains do not react with anti-Lewis x (Le^x) monoclonal antibodies (MAbs) while structurally they were shown to express Le^x (39). Thus, Lewis antigen expression in H. pylori is highly conserved. This restricted diversity in O-antigen structure is striking, and the question arises whether H. pylori Lewis antigens play a role in pathogenesis. An analogous situation is found in Neisseria gonorrhoeae, where conserved LPS O-antigen epitopes directly interact with the host via ligand-lectin binding (35).

There are additional reasons why H. pylori LPS Lewis antigens are thought to play a role in pathogenesis beyond merely providing length to the LPS (although length itself already contributes to virulence) (7). (i) H. pylori LPS displays phase variation, defined as the high frequency of reversible change of LPS phenotype (2, 5, 68, 69). In other bacteria (Neisseria spp. and Haemophilus influenzae), phase variation of LPS is crucial to virulence (37, 65). (ii) H. pylori LPS displays molecular mimicry with the host (4). Gastric human epithelial cells also express Le^x/y blood group antigens. The expression by microorganisms of surface structures similar to those found in the host is called molecular mimicry. Examples of other pathogens displaying molecular mimicry are Campylobacter jejuni and Neisseria spp. (33). The role of mimicry in pathogenesis can be twofold. (a) H. pylori mimicry is pathogenic. Infection might break tolerance to the shared epitopes and induce autoantibodies. Bound antibodies may induce tissue damage, for instance, by fixing complement. (b) Molecular mimicry might provide immune escape by preventing the formation of antibodies directed to the epitopes shared by self and microorganism; the lack of response to a surface-located antigen might contribute to persistence of infection. (iii) H. pylori Lewis antigens might interact with host lectins. Several host lectins are known to interact with host Lewis antigens (22, 42); the same lectins may interact with H. pylori Lewis antigens. Such interaction may have biological consequences such as bacterial adhesion, colonization, and cytokine induction.

In this chapter, we will discuss phase variation of H. pylori LPS, including LPS biosynthesis and genetics; the biological significance of Lewis antigen mimicry; and the role of Lewis antigens in interactions of H. pylori with host lectins.