T cells activated by zwitterionic molecules prevent abscesses induced by pathogenic bacteria

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Bacterial polysaccharides are typically classified as T cell-independent antigens.
• Existing models do not explain the T cell-dependent protection conferred by zwitterionic polysaccharides (Zps) against intraabdominal abscesses.

Purpose of the Study:

• To investigate the mechanism by which Zps elicit T cell-dependent immune responses.
• To determine if Zps can activate CD4+ T cells and confer protection against bacterial infections.

Main Methods:

• In vitro stimulation of CD4+ T cells with Zps and modified Zps.
• Assessment of major histocompatibility complex class II molecule involvement.
• Synthesis and testing of zwitterionic charge motif mimicking peptides.
• In vivo adoptive transfer of stimulated T cells in a rat abscess model.

Main Results:

• Zps induced a potent CD4+ T cell response in vitro, dependent on major histocompatibility complex class II.
• Specific chemical modifications revealed the importance of carbohydrate structure and free amino/carboxyl groups.
• Lysine-aspartic acid peptides mimicking the zwitterionic motif stimulated T cells and protected against abscesses.
• Adoptive transfer of human T cells stimulated by Zps conferred protection against bacterial-induced abscesses in rats.

Conclusions:

• Bacterial polysaccharides with a zwitterionic charge motif can activate T cells.
• This T cell activation provides immunity against intraabdominal abscess formation.
• Zwitterionic polysaccharides represent a novel class of T cell-activating antigens with therapeutic potential.