KIR3DL1 and Tox identify clonally expanded encephalitogenic neuron-specific CD8+ T cells in autoimmune encephalitis
Perriot, S.; Jones, S.; Genolet, R.; Mathias, A.; Lindsay, H.; Bobisse, S.; Di Liberto, G.; Canales, M.; Queiroz, L.; Sauvage, C.; Wagner, I.; Oberholster, L.; Gimenez, M.; Begarie, D.; Theaudin, M.; Pot, C.; Merkler, D.; Gottardo, R.; Harari, A.; Du Pasquier, R.
Show abstract
Autoreactive CD8+ T cells are the principal suspects in autoimmune encephalitis (AIE) with antibodies targeting intracellular neuronal antigens So far, the search for neuron-autoreactive CD8+ T cells has been focused on a few autoantigens and did not yield convincing results. Here, we leveraged natural antigen presentation by hiPSC-derived neurons to look at the global autoreactive CD8+ T cell response, independently of pre-conceived hypothesis of the autoantigens involved in the disease. This unbiased approach allowed for the identification of rare polyclonal neuron-reactive CD8+ T cells in healthy donors, and contrastingly, expanded clonotypes in two patients with anti-Ri AIE. Detailed ex vivo phenotypic characterization of these clonotypes revealed a specific transcriptional program suggestive of a pathogenic potential. In particular, this subset can be identified by the expression of KIR3DL1 and TOX. Strikingly, we could also demonstrate that CD8+ T cells found in the brain of an anti-Ri AIE patient display a similar phenotype associated with cytotoxicity and encephalitogenic features.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- TCR repertoire profiling revealed antigen-driven CD8+ T cell clonal groups shared in synovial fluid of patients with spondyloarthritis 95%
- Augmented expansion of Treg cells from healthy and autoimmune subjects via adult progenitor cell co-culture. 94%
- Gene expression-based identification of antigen-responsive CD8+ T cells on a single-cell level 94%
Similar papers in this journal
- Stereotyped B-cell responses are linked to IgG constant region polymorphisms in multiple sclerosis 94%
- Follicular helper T cell signature of replicative exhaustion, apoptosis and senescence in common variable immunodeficiency 94%
- Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing 94%
Similar papers in this journal
- Rewired type I IFN signaling is linked to age-dependent differences in COVID-19 93%
- COVID-19 convalescents exhibit deficient humoral and T cell responses to variant of concern Spike antigens at 12 month post-infection 93%
- Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases 93%
Similar papers in this journal
- Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells. 95%
- Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children 95%
- Impaired antigen-specific memory B cell and plasma cell responses including lack of specific IgG upon SARS-CoV-2 BNT162b2 vaccination among Kidney Transplant and Dialysis patients 95%
Similar papers in this journal
"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.