Hydrophobic CDR3 residues promote the development of self-reactive T cells
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Hydrophobic CDR3.pdf
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Author(s)
Stadinski, Brian D
Shekhar, Karthik
Gómez-Touriño, Iria
Jung, Jonathan
Sasaki, Katsuhiro
Sewell, Andrew K
Peakman, Mark
Chakraborty, Arup K
Huseby, Eric S
Date Issued
June 2016
Journal
Nature Immunology
Publisher
Nature Publishing Group
Citation
Stadinski, Brian D et al. “Hydrophobic CDR3 Residues Promote the Development of Self-Reactive T Cells.” Nature Immunology 17.8 (2016): 946–955.
Version
Author's final manuscript
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 (V[subscript β]) family present in the TCR or the length of the CDR3β. An index based on these findings distinguished V[subscript β]2[superscript +], V[subscript β]6[superscript +] and V[subscript β]8.2[superscript +] regulatory T cells from conventional T cells and also distinguished CD4[superscript +] T cells selected by the major histocompatibility complex (MHC) class II molecule I-A[superscript 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-Ab. Our results provide a means for distinguishing normal T cell repertoires versus autoimmunity-prone T cell repertoires.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Physics
Ragon Institute of MGH, MIT and Harvard
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DOI of Published Version
https://doi.org/10.1038/ni.3491
