Polysaccharide A from the Capsule of Bacteroides fragilis Induces Clonal CD4+ T Cell Expansion |
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Authors: | Jenny L. Johnson Mark B. Jones Brian A. Cobb |
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Affiliation: | From the Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 |
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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+CD45RBlow 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. |
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Keywords: | Glycobiology Immunology Lymphocyte Major Histocompatibility Complex (MHC) Polysaccharide |
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