Polysaccharide A from the capsule of Bacteroides fragilis induces clonal CD4+ T cell expansion

J Biol Chem. 2015 Feb 20;290(8):5007-5014. doi: 10.1074/jbc.M114.621771. Epub 2014 Dec 24.


For 3 decades, the view of MHCII-dependent antigen presentation has been completely dominated by peptide antigens despite our 2004 discovery in which MHCII was shown to present processed fragments of zwitterionic capsular polysaccharides to T cells. Published findings further demonstrate that polysaccharide A (PSA) from the capsule of Bacteroides fragilis is a potent activator of CD4(+) T cells and that these T cells have important biological functions, especially in the maintenance of immunological homeostasis. However, little is known about the nature of T cell recognition of the polysaccharide-MHCII complex or the phenotype of the resulting activated cells. Here, we use next-generation sequencing of the αβT cell receptor of CD4(+) T cells from mice stimulated with PSA in comparison with protein antigen simulation and non-immunized controls and found that PSA immunization induced clonal expansion of a small subset of suppressive CD4(+)CD45RB(low) effector/memory T cells. Moreover, the sequences of the complementarity-determining region 3 (CDR3) loop from top clones indicate a lack of specific variable β and joining region use and average CDR3 loop length. There was also a preference for a zwitterionic motif within the CDR3 loop sequences, aligning well with the known requirement for a similar motif within PSA to enable T cell activation. These data support a model in which PSA, and possibly other T cell-dependent polysaccharide antigens, elicits a clonal and therefore specific CD4(+) T cell response often characterized by pairing dual-charged CDR3 loop sequences with dual-charged PSA.

Keywords: Glycobiology; Immunology; Lymphocyte; Major Histocompatibility Complex (MHC); Polysaccharide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Capsules / chemistry*
  • Bacteroides fragilis / chemistry*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Complementarity Determining Regions / immunology
  • Immunologic Memory / drug effects
  • Lymphocyte Activation / drug effects*
  • Mice
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / pharmacology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology


  • Complementarity Determining Regions
  • Polysaccharides, Bacterial
  • Receptors, Antigen, T-Cell, alpha-beta