Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease
Satoshi Nozuma, Yoshimi Enose-Akahata, Kory R. Johnson, Maria Chiara Monaco, Nyater Ngouth, Abdel Elkahloun, Joan Ohayon, Jun Zhu, Steven Jacobson
Satoshi Nozuma, Yoshimi Enose-Akahata, Kory R. Johnson, Maria Chiara Monaco, Nyater Ngouth, Abdel Elkahloun, Joan Ohayon, Jun Zhu, Steven Jacobson
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Research Article Immunology Infectious disease

Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease

Abstract

In this study, we examined and characterized disease-specific TCR signatures in cerebrospinal fluid (CSF) of patients with HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). TCR β libraries using unique molecular identifier–based methodologies were sequenced in paired peripheral blood mononuclear cells (PBMCs) and CSF cells from HAM/TSP patients and normal healthy donors (NDs). The sequence analysis demonstrated that TCR β repertoires in CSF of HAM/TSP patients were highly expanded and contained both TCR clonotypes shared with PBMCs and uniquely enriched within the CSF. In addition, we analyzed TCR β repertoires of highly expanded and potentially immunopathologic HTLV-1 Tax11-19–specific CD8+ T cells from PBMCs of HLA-A*0201+ HAM/TSP and identified a conserved motif (PGLAG) in the CDR3 region. Importantly, TCR β clonotypes of expanded clones in HTLV-1 Tax11-19–specific CD8+ T cells were also expanded and enriched in the CSF of the same patient. These results suggest that exploring TCR repertoires of CSF and antigen-specific T cells may provide a TCR repertoire signature in virus-associated neurologic disorders.

Authors

Satoshi Nozuma, Yoshimi Enose-Akahata, Kory R. Johnson, Maria Chiara Monaco, Nyater Ngouth, Abdel Elkahloun, Joan Ohayon, Jun Zhu, Steven Jacobson

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Figure 6

Enrichment of Tax-specific TCR β expanded clonotypes in CSF of a HAM/TSP patient.

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Enrichment of Tax-specific TCR β expanded clonotypes in CSF of a HAM/TSP...
(A) T cell clonal expansion of sorted Tax11-19–specific CD8+ T cells from PBMCs (left), PBMCs (middle), and CSF (right) of a HAM/TSP patient (HAM-6). TCR β clonal expansion was analyzed by using the frequency of clones ≥ 8 UMIs (colored wedges), clones with 2 ≤ UMIs < 8 (gray), and singletons (white). In the group of expanded clones, each wedge represents a unique clonotype with a defined CDR3 sequence, and the same clone shared among Tax11-19–specific CD8+ T cells, PBMCs, and CSF cells is visualized in the same color. (B) Frequencies of 7 TCR β expanded clonotypes of Tax11-19–specific CD8+ T cells in PBMCs and CSF of a HAM-TSP patients (HAM-6). Each clonotype is visualized in the same color with the wedge of the pie chart in A.