Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease

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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