Antigen-specificity of clonally-enriched CD8+ T cells in multiple sclerosis
Mittl, K.; Hayashi, F.; Dandekar, R.; Schubert, R. D.; Gerdts, J.; Oshiro, L.; Loudermilk, R.; Greenfield, A. L.; Augusto, D. G.; Ramesh, A.; Tran, E.; Koshal, K.; Kizer, K.; Dreux, J.; Cagalingan, A.; Schustek, F.; Flood, L.; Moore, T.; Kirkemo, L. L.; Cooper, T.; Harms, M.; Gomez, R.; University of California, San Francisco MS-EPIC Team, ; Sibener, L.; Cree, B. A. C.; Hauser, S. L.; Hollenbach, J. A.; Gee, M.; Wilson, M. R.; Zamvil, S.; Sabatino, J. J.
Show abstract
CD8+ T cells are the dominant lymphocyte population in multiple sclerosis (MS) lesions where they are highly clonally expanded. The clonal identity, function, and antigen specificity of CD8+ T cells in MS are not well understood. Here we report a comprehensive single-cell RNA-seq and T cell receptor (TCR)-seq analysis of the cerebrospinal fluid (CSF) and blood from a cohort of treatment-naive MS patients and control participants. A small subset of highly expanded and activated CD8+ T cells were enriched in the CSF in MS that displayed high activation, cytotoxicity and tissue-homing transcriptional profiles. Using a combination of unbiased and targeted antigen discovery approaches, MS-derived CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. These findings shed vital insight into the role of CD8+ T cells in MS and pave the way towards disease biomarkers and therapeutic targets. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/611010v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a0b738org.highwire.dtl.DTLVardef@5cf5c2org.highwire.dtl.DTLVardef@10abdccorg.highwire.dtl.DTLVardef@32c7b2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical SummaryC_FLOATNO Created in BioRender. Sabatino, J. (2024) BioRender.com/e66l598 C_FIG
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis 96%
- A framework to identify antigen-expanded T Cell Receptor (TCR) clusters within complex repertoires 95%
- A single-cell atlas of lymphocyte adaptive immune repertoires and transcriptomes reveals age-related differences in convalescent COVID-19 patients 95%
Similar papers in this journal
- Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity 97%
- Probing the basis of disease heterogeneity in multiple sclerosis using genetically diverse mice 96%
- Rapamycin rescues loss-of-function in blood-brain barrier-interacting regulatory T cells 95%
Similar papers in this journal
- Impact of genetic susceptibility to multiple sclerosis on the T cell epigenome: proximal and distal effects 95%
- Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases 95%
- Single-cell transcriptomics identifies drivers of local inflammation in multiple sclerosis 94%
Similar papers in this journal
- Profiling of small non-coding RNAs across cellular and biofluid compartments: implications for multiple sclerosis immunopathology 96%
- Turncoat antibodies unmasked in a model of autoimmune demyelination: from biology to therapy 95%
- CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity 95%
Similar papers in this journal
- MHC class I and MHC class II reporter mice enable analysis of immune oligodendroglia in mouse models of multiple sclerosis 96%
- Spatial Transcriptomics of Meningeal Inflammation Reveals Inflammatory Gene Signatures in Adjacent Brain Parenchyma 95%
- Single-cell profiling reveals periventricular CD56bright NK cell accumulation in multiple sclerosis 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.