title: Polysaccharide A from the capsule of Bacteroides fragilis induces clonal CD4+ T cell expansion.
abstract: 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.
authors.affiliation: From the Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Johnson
authors.affiliation: From the Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Jones
authors.affiliation: From the Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106. Electronic address: brian.cobb@case.edu.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Cobb
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000737:chemistry*; D001441:Bacteroides fragilis / Q000737:chemistry*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology
chemical_list: D022801:Complementarity Determining Regions; D011135:Polysaccharides, Bacterial; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Glycobiology; Immunology; Lymphocyte; Major Histocompatibility Complex (MHC); Polysaccharide