title: Hydrophobic CDR3 residues promote the development of self-reactive T cells.
abstract: Studies of individual T cell antigen receptors (TCRs) have shed some light on structural features that underlie self-reactivity. However, the general rules that can be used to predict whether TCRs are self-reactive have not been fully elucidated. Here we found that the interfacial hydrophobicity of amino acids at positions 6 and 7 of the complementarity-determining region CDR3β robustly promoted the development of self-reactive TCRs. This property was found irrespective of the member of the β-chain variable region (Vβ) family present in the TCR or the length of the CDR3β. An index based on these findings distinguished Vβ2(+), Vβ6(+) and Vβ8.2(+) regulatory T cells from conventional T cells and also distinguished CD4(+) T cells selected by the major histocompatibility complex (MHC) class II molecule I-A(g7) (associated with the development of type 1 diabetes in NOD mice) from those selected by a non-autoimmunity-promoting MHC class II molecule I-A(b). Our results provide a means for distinguishing normal T cell repertoires versus autoimmunity-prone T cell repertoires.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School Worcester, Massachusetts, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Stadinski
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Shekhar
authors.affiliation: Department of Immunobiology, King's College London, London, UK.
authors.forename: Iria
authors.initials: I
authors.lastname: Gómez-Touriño
authors.affiliation: Department of Pathology, University of Massachusetts Medical School Worcester, Massachusetts, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Pathology, University of Massachusetts Medical School Worcester, Massachusetts, USA.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sewell
authors.affiliation: Department of Immunobiology, King's College London, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Peakman
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Arup K
authors.initials: AK
authors.lastname: Chakraborty
authors.affiliation: Department of Pathology, University of Massachusetts Medical School Worcester, Massachusetts, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Huseby
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D002454:Cell Differentiation; D061167:Central Tolerance; D022801:Complementarity Determining Regions / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D001324:Autoantigens; D022801:Complementarity Determining Regions; D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen; C474482:I-A(b) antigen, mouse