Polysaccharide epitopes recognized by human α-L-Rha antibodies.

The levels of antibodies in human blood binding to the monosaccharide α-L-Rha are the highest among all anti-glycan antibodies. Moreover, anti-Rha antibodies are found in all individuals, suggesting that they are naturally occurring rather than adaptive immunoglobulins. Rhamnose is common in both bacterial (especially infectious) and plant polysaccharides, however, it remains poorly understood which rhamnose-containing epitope(s) - whether monosaccharide, oligosaccharide, or complex molecular patterns - are recognized by human antibodies. Using an affinity adsorbent, α-L-Rha-Sepharose, antibodies were isolated from human immunoglobulin preparations (IgG + IgM + IgA) and analyzed using highly representative arrays of bacterial and plant polysaccharides (about 1000 glycans, of which >240 contained Rha). Isolated anti-α-L-Rha antibodies bound to almost all polysaccharides where the rhamnose residue was located either terminally or as α1-2, 1-3 or 1-4 linked pendant substituent, but not to internal positions, regardless of whether they were bacterial O-antigens or plant polysaccharides. It was concluded that human polyclonal anti-α-L-Rha antibodies have a reasonably narrow range of epitope specificity. The recognition of a small-sized monosaccharide epitope, on one hand, and a high proportion of IgM and IgA, on the other, suggest a high degree of polyvalence in recognizing the natural targets of the antibodies studied. In vivo, anti-α-L-Rha antibodies are more likely to recognize a pattern composed of tightly packed lipopolysaccharides (or capsular polysaccharides, or plant cell walls) rather than repetitive epitopes on a single polysaccharide molecule.