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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 ? 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 ? 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 ? 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 ? 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.

SUBMITTER: Nozuma S 

PROVIDER: S-EPMC7934934 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease.

Nozuma Satoshi S   Enose-Akahata Yoshimi Y   Johnson Kory R KR   Monaco Maria Chiara MC   Ngouth Nyater N   Elkahloun Abdel A   Ohayon Joan J   Zhu Jun J   Jacobson Steven S  

JCI insight 20210222 4


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 expa  ...[more]

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