T-cell repertoire profiling by next-generation sequencing reveals tissue migration dynamics of TRBV13-family clonotypes in a common experimental autoimmune encephalomyelitis mouse model

J Neuroimmunol. 2019 Jul 15:332:49-56. doi: 10.1016/j.jneuroim.2019.03.014. Epub 2019 Mar 23.

Abstract

The experimental autoimmune encephalomyelitis (EAE) model is indispensable for autoimmunity research, but model-specific T cell dynamics are sparsely studied. We used next-generation immunosequencing across lymphoid organs, blood and spinal cord in response to immunization with myelin basic protein (MBP) to study T cell repertoires and migration patterns. Surprisingly, most spinal cord T cells were unique to the individual animal despite the existence of shared MBP-specific clones, suggesting a previously underestimated T cell diversity. Almost complete emigration of pathogenic clones from blood to spinal cord indicates that blood is not a suitable compartment to study EAE-mediating T cells.

Keywords: Experimental autoimmune encephalomyelitis; Immunosequencing; Next-generation sequencing; T-cell repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Blood Cells / immunology
  • Blood Cells / pathology
  • Cell Movement
  • Clonal Selection, Antigen-Mediated / genetics*
  • Clone Cells / immunology
  • Encephalomyelitis, Autoimmune, Experimental / blood
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • High-Throughput Nucleotide Sequencing
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / pathology
  • Mice
  • Myelin Basic Protein / immunology
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Specific Pathogen-Free Organisms
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • T-Cell Antigen Receptor Specificity / genetics*
  • T-Lymphocyte Subsets / immunology*

Substances

  • Autoantigens
  • Mbp protein, mouse
  • Myelin Basic Protein
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta