Effect of molecular size on the ability of zwitterionic polysaccharides tostimulate cellular immunity

The large-molecular-sized zwitterionic capsular polysaccharide of the anaer obe Bacteroides fragilis NCTC 9343, designated polysaccharide (PS) A, stimu lates T cell proliferation in vitro and induces T cell-dependent protection against abscess formation in vivo. In the present study, we utilized a mod ification of a recently developed ozonolytic method for depolymerizing poly saccharides to examine the influence of the molecular size of PS A on cell- mediated immunity. Ozonolysis successfully depolymerized PS A into structur ally intact fragments. PS A with average molecular sizes of 129.0 (native), 77.8, 46.9, and 17.1 kDa stimulated CD4(+)-cell proliferation in vitro to the same degree, whereas the 5.0-kDa fragment was much less stimulatory tha n the control 129.0-kDa PS A. Rats treated with 129.0-kDa, 46.9-kDa, and 17 .1-kDa PS A molecules, but not those treated with the 5.0-kDa molecule, wer e protected against intraabdominal abscesses induced by challenge with viab le B, fragilis, These results demonstrate that a zwitterionic polysaccharid e as small as 22 repeating units (88 monosaccharides) elicits a T cell-depe ndent immune response. These findings clearly distinguish zwitterionic T ce ll-dependent polysaccharides from T-cell-independent polysaccharides and gi ve evidence of the existence of a novel mechanism for a polysaccharide-indu ced immune response.