title: Tetramers reveal IL-17-secreting CD4+ T cells that are specific for U1-70 in lupus and mixed connective tissue disease.
abstract: Antigen-specific CD4(+) T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about the peptide antigens that they recognize and their precise function in disease. We generated a series of MHC class II tetramers of I-E(k)-containing peptides from the spliceosomal protein U1-70 that specifically stain distinct CD4(+) T-cell populations in MRL/lpr mice. The T-cell populations recognize an epitope differing only by the presence or absence of a single phosphate residue at position serine(140). The frequency of CD4(+) T cells specific for U1-70(131-150):I-E(k) (without phosphorylation) correlates with disease severity and anti-U1-70 autoantibody production. These T cells also express RORγt and produce IL-17A. Furthermore, the U1-70-specific CD4(+) T cells that produce IL-17A are detected in a subset of patients with SLE and are significantly increased in patients with mixed connective tissue disease. These studies provide tools for studying antigen-specific CD4(+) T cells in lupus, and demonstrate an antigen-specific source of IL-17A in autoimmune disease.
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine and.
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Kattah
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine and.
authors.forename: Justin Ansel
authors.initials: JA
authors.lastname: Jarrell
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine and.
authors.forename: Alvina D
authors.initials: AD
authors.lastname: Chu
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xie
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine and.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kattah
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Ofir
authors.initials: O
authors.lastname: Goldberger
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine and.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ye
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine and.
authors.forename: Eliza F
authors.initials: EF
authors.lastname: Chakravarty
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 mmdavis@stanford.edu pjutz@stanford.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine and mmdavis@stanford.edu pjutz@stanford.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Utz
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008947:Mixed Connective Tissue Disease / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology*; D010766:Phosphorylation
chemical_list: D001323:Autoantibodies; D020381:Interleukin-17; D009842:Oligopeptides
keywords: IL-17; SLE; autoimmunity; lupus; tetramer