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The Journal of Immunology, 2000, 164: 719-724.
Copyright © 2000 by The American Association of Immunologists

Effect of Molecular Size on the Ability of Zwitterionic Polysaccharides to Stimulate Cellular Immunity1

Wiltrud M. Kalka-Moll*, Arthur O. Tzianabos*, Ying Wang*, Vincent J. Carey*, Robert W. Finberg§, Andrew B. Onderdonk*,{dagger} and Dennis L. Kasper2,*,{ddagger}

Departments of * Medicine, {dagger} Pathology, and {ddagger} Microbiology and Molecular Genetics, Channing Laboratory, Brigham and Women’s Hospital, and § Division of Infectious Disease, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115

The large-molecular-sized zwitterionic capsular polysaccharide of the anaerobe Bacteroides fragilis NCTC 9343, designated polysaccharide (PS) A, stimulates T cell proliferation in vitro and induces T cell-dependent protection against abscess formation in vivo. In the present study, we utilized a modification of a recently developed ozonolytic method for depolymerizing polysaccharides to examine the influence of the molecular size of PS A on cell-mediated immunity. Ozonolysis successfully depolymerized PS A into structurally 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 than 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, were protected against intraabdominal abscesses induced by challenge with viable B. fragilis. These results demonstrate that a zwitterionic polysaccharide as small as 22 repeating units (88 monosaccharides) elicits a T cell-dependent immune response. These findings clearly distinguish zwitterionic T cell-dependent polysaccharides from T cell-independent polysaccharides and give evidence of the existence of a novel mechanism for a polysaccharide-induced immune response.




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