Human Antibody Response to Helicobacter pylori Lipopolysaccharide: Presence of an Immunodominant Epitope in the Polysaccharide Chain of Lipopolysaccharide

We have examined the antibody response to Helicobacter pylori lipopolysaccharides (LPS) in humans. We used sera from patients with gastroduodenal diseases and healthy adults infected or not infected with H. pylori. Data from the experiments for antibody binding to LPS suggested that the polysaccharide chains from many H. pylori strains showed high immunogenicity in humans. Sera from most (above 70%) H. pylori-infected individuals contained immunoglobulin G (IgG) antibodies against the polysaccharide region highly immunogenic H. pylori LPS. The IgG titers of individual serum samples that reacted strongly with highly immunogenic LPS were quite similar (r(2) = 0.84 to 0.98). The results suggest wide distribution among H. pylori strains of a highly antigenic epitope in the polysaccharide moieties of their LPS. Also, the similarity in the titers of individual serum samples against highly immunogenic LPS points to the existence of epitopes sharing a common structural motif. However, some strains showed low antigenicity, even those with polysaccharide-carrying LPS. The dominant subclass of IgG that reacted with the highly immunogenic LPS was IgG2, which was preferentially raised against polysaccharide antigens. Recently, a structure that mimics that of the Lewis antigens was identified in the O-polysaccharide fraction of H. pylori LPS; however, no correlation between antigenicity of the polysaccharide chain in humans and the presence of Lewis antigens was found. The IgA and IgM titers against H. pylori LPS seemed to be mostly nonspecific and directed against lipid A. In a few cases, however, sera from individuals infected with H. pylori gave strong IgA and IgM titers against the highly immunogenic polysaccharide. In conclusion, the LPS of many H. pylori strains possess an antigenic epitope in their polysaccharide regions that is immunogenic in humans. However, our results show that the antigenic epitope is unlikely to be immunologically related to structures mimicking Lewis antigens.

本研究针对人类针对幽门螺杆菌（Helicobacter pylori）脂多糖（lipopolysaccharides, LPS）的抗体应答开展了系统性分析。本研究使用了罹患胃十二指肠疾病的患者，以及感染或未感染幽门螺杆菌的健康成人的血清样本。抗体结合脂多糖的实验数据显示，多数幽门螺杆菌菌株的多糖链在人体内具有较高免疫原性。超过70%的幽门螺杆菌感染者血清中，均含有针对高免疫原性幽门螺杆菌脂多糖多糖区域的免疫球蛋白G（immunoglobulin G, IgG）抗体。与高免疫原性脂多糖发生强结合反应的单个血清样本，其IgG抗体滴度均较为接近（决定系数r²=0.84~0.98）。上述结果表明，多数幽门螺杆菌菌株的脂多糖多糖结构域中，广泛存在高抗原性表位。此外，不同感染者血清针对高免疫原性脂多糖的抗体滴度相似性，提示存在共享共同结构基序的表位。但部分携带多糖结构脂多糖的幽门螺杆菌菌株，其抗原性却相对较弱。与高免疫原性脂多糖结合的IgG主要亚类为IgG2，该亚类通常优先由多糖抗原诱导产生。近期研究在幽门螺杆菌脂多糖的O-多糖组分中，发现了模拟路易斯抗原（Lewis antigens）的结构；但未观察到人体中多糖链的抗原性与路易斯抗原存在之间存在相关性。针对幽门螺杆菌脂多糖的IgA与IgM抗体滴度，多数情况下为非特异性结合，且靶向脂质A（lipid A）结构域。但在少数病例中，幽门螺杆菌感染者的血清可针对高免疫原性多糖产生较高滴度的IgA与IgM抗体。综上，多数幽门螺杆菌菌株的脂多糖多糖区域，均存在可在人体中诱导免疫应答的抗原性表位；但本研究结果表明，该抗原性表位与模拟路易斯抗原的结构不存在免疫学关联。