Immunologic paradigms classify
bacterial polysaccharides as T cell-independent
antigens. However, these models fail to explain how zwitterionic
polysaccharides (Zps) confer protection against intraabdominal
abscess formation in a T cell-dependent manner. Here, we demonstrate that Zps elicit a potent CD4+ T cell response in vitro that requires available major histocompatibility complex class II molecules on antigen-presenting cells. Specific chemical modifications to Zps show that: 1) the activity is specific for
carbohydrate structure, and 2) the proliferative response depends upon free amino and carboxyl groups on the repeating units of these
polysaccharides.
Peptides synthesized to mimic the zwitterionic charge motif associated with Zps also exhibited these
biologic properties.
Lysine-
aspartic acid (KD)
peptides with more than 15 repeating units stimulated CD4+ T cells in vitro and conferred protection against
abscesses induced by bacteria such as Bacteroides fragilis and Staphylococcus aureus. Evidence for the
biologic importance of T cell activation by these zwitterionic
polymers was provided when human CD4+ T cells stimulated with these molecules in vitro and adoptively transferred to rats in vivo conferred protection against intraabdominal
abscesses induced by viable bacterial challenge. These studies demonstrate that
bacterial polysaccharides with a distinct charge motif activate T cells and that this activity confers immunity to a distinct pathologic response to
bacterial infection.