title: Discovery of T Cell Receptor β Motifs Specific to HLA-B27-Positive Ankylosing Spondylitis by Deep Repertoire Sequence Analysis.
abstract: Ankylosing spondylitis (AS), a chronic inflammatory disorder, has a notable association with HLA-B27. One hypothesis suggests that a common antigen that binds to HLA-B27 is important for AS disease pathogenesis. This study was undertaken to determine sequences and motifs that are shared among HLA-B27-positive AS patients, using T cell repertoire next-generation sequencing.
  
  
  
  To identify motifs enriched among B27-positive AS patients, we performed T cell receptor β (TCRβ) repertoire sequencing on samples from 191 B27-positive AS patients, 43 B27-negative AS patients, and 227 controls, and we obtained >77 million TCRβ clonotype sequences. First, we assessed whether any of 50 previously published sequences were enriched in B27-positive AS patients. We then used training and test cohorts to identify discovered motifs that were enriched in B27-positive AS patients versus controls.
  
  
  
  Six previously published and 11 discovered motifs were enriched in the B27-positive AS samples as compared to controls. After combining motifs related by sequence, we identified a total of 15 independent motifs. Both the full set of 15 motifs and a set of 6 published motifs were enriched in the B27-positive AS patients as compared to B27-positive healthy individuals (P = 0.049 and P = 0.001, respectively). Using an independent cohort, we validated that at least some of these motifs were associated with AS, and not simply with B27-positive status.
  
  
  
  We identified TCRβ motifs that are enriched in B27-positive AS patients as compared to B27-positive healthy controls. This suggests that a common antigen, presented by HLA-B27 and detected by CD8+ T cells, may be associated with AS disease pathogenesis.
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Victoria
authors.initials: V
authors.lastname: Carlton
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Martin
authors.initials: M
authors.lastname: Moorhead
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Mark
authors.initials: M
authors.lastname: Klinger
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Francois
authors.initials: F
authors.lastname: Pepin
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Thomas
authors.initials: T
authors.lastname: Asbury
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Marissa
authors.initials: M
authors.lastname: Vignali
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation, Seattle, Washington.
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Emerson
authors.affiliation: Adaptive Biotechnologies Corporation, South San Francisco, California, and Adaptive Biotechnologies Corporation and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Harlan S
authors.initials: HS
authors.lastname: Robins
authors.affiliation: Alternate Allele Consulting, Orinda, California.
authors.forename: James
authors.initials: J
authors.lastname: Ireland
authors.affiliation: University of Minnesota, Minneapolis.
authors.forename: Emily
authors.initials: E
authors.lastname: Baechler-Gillespie
authors.affiliation: Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
mesh_terms: D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D005260:Female; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D017421:Sequence Analysis; D013167:Spondylitis, Ankylosing / Q000276:immunology*; D055815:Young Adult
chemical_list: D015796:HLA-B27 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta