title: Autoimmune susceptibility imposed by public TCRβ chains.
abstract: Although the TCR repertoire is highly diverse, a small fraction of TCR chains, referred to as public, preferentially form and are shared by most individuals. Prior studies indicated that public TCRβ may be preferentially deployed in autoimmunity. We hypothesized that if these TCRβ modulate the likelihood of a TCRαβ heterodimer productively engaging autoantigen, because they are widely present in the population and often high frequency within individual repertoires, they could also broadly influence repertoire responsiveness to specific autoantigens. We assess this here using a series of public and private TCRβ derived from autoimmune encephalomyelitis-associated TCR. Transgenic expression of public, but not private, disease-associated TCRβ paired with endogenously rearranged TCRα endowed unprimed T cells with autoantigen reactivity. Further, two of six public, but none of five private TCRβ provoked spontaneous early-onset autoimmunity in mice. Our findings indicate that single TCRβ are sufficient to confer on TCRαβ chains reactivity toward disease-associated autoantigens in the context of diverse TCRα. They further suggest that public TCR can skew autoimmune susceptibility, and that subsets of public TCR sequences may serve as disease- specific biomarkers or therapeutic targets.
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Phuong
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Bofeng
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Lindsay L
authors.initials: LL
authors.lastname: Jones
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Terrence L
authors.initials: TL
authors.lastname: Geiger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D055503:Protein Multimerization; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D016693:Receptors, Antigen, T-Cell, alpha-beta