title: TCR sequencing of single cells reactive to DQ2.5-glia-α2 and DQ2.5-glia-ω2 reveals clonal expansion and epitope-specific V-gene usage.
abstract: CD4+ T cells recognizing dietary gluten epitopes in the context of disease-associated human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 molecules are the key players in celiac disease pathogenesis. Here, we conducted a large-scale single-cell paired T-cell receptor (TCR) sequencing study to characterize the TCR repertoire for two homologous immunodominant gluten epitopes, DQ2.5-glia-α2 and DQ2.5-glia-ω2, in blood of celiac disease patients after oral gluten challenge. Despite sequence similarity of the epitopes, the TCR repertoires are unique but shared several overall features. We demonstrate that clonally expanded T cells dominate the T-cell responses to both epitopes. Moreover, we find V-gene bias of TRAV26, TRAV4, and TRBV7 in DQ2.5-glia-α2 reactive TCRs, while DQ2.5-glia-ω2 TCRs displayed significant bias toward TRAV4 and TRBV4. The knowledge that antigen-specific TCR repertoire in chronic inflammatory diseases tends to be dominated by a few expanded clones that use the same TCR V-gene segments across patients is important information for HLA-associated diseases where the antigen is unknown.
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Dahal-Koirala
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: L F
authors.initials: LF
authors.lastname: Risnes
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Christophersen
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: V K
authors.initials: VK
authors.lastname: Sarna
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.|Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: K Ea
authors.initials: KE
authors.lastname: Lundin
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: L M
authors.initials: LM
authors.lastname: Sollid
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: S W
authors.initials: SW
authors.lastname: Qiao
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated; D004247:DNA / Q000032:analysis*; D005983:Glutens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D059010:Single-Cell Analysis
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell; D005983:Glutens; D004247:DNA
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