Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 290, Issue 8, Pages 5007-5014Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.621771
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Funding
- National Institutes of Health [GM082916, OD004225]
- American Asthma Foundation [10-0187]
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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 alpha beta T 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 beta and joining region use and average CDR3loop 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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