Single-cell immune repertoire sequencing of B and T cells in murine models of infection and autoimmunity

• Published in: bioRxiv
• Main Authors: Shlesinger, Danielle, Kai-Lin, Hong, Shammas, Ghazal, Page, Nicolas, Sandu, Ioana, Agrafiotis, Andreas, Kreiner, Victor, Fonta, Nicolas, Vincenti, Ilena, Wagner, Ingrid, Piccinno, Margot, Mariotte, Alexandre, Klimek, Bogna, Dizerens, Raphael, Manero-Carranza, Marcos, Kuhn, Raphael, Ehling, Roy, Frei, Lester, Khodaverdi, Keywan, Panetti, Camilla, Joller, Nicole, Oxenius, Annette, Merkler, Doron, Reddy, Sai T, Yermanos, Alexander
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 10.02.2022
• Subjects: Animal models; Autoimmune diseases; Autoimmunity; CD8 antigen; Cell activation; Cell culture; Chronic infection; Clonal selection; Computer applications; Experimental allergic encephalomyelitis; Helper cells; Immunological memory; Infections; Lymphocytes; Lymphocytes T; Memory cells; Nervous system; Phenotypes; Scholarly publishing; T cell receptors; Transcription; Transcriptomes; Viral infections
• DOI: 10.1101/2022.02.07.479381

Adaptive immune repertoires are composed by the ensemble of B and T cell receptors (BCR, TCR) within an individual and reflect both past and current immune responses. Recent advances in single-cell sequencing enable recovery of the complete adaptive immune receptor sequences in addition to transcriptional information. Such high-dimensional datasets enable the molecular quantification of clonal selection of B and T cells across a wide variety of conditions such as infection and disease. Due to costs, time required for the analysis and current practices of academic publishing, small-scale sequencing studies are often not made publicly available, despite having informative potential to elucidate immunological principles and guide future-studies. Here, we performed single-cell sequencing of B and T cells to profile clonal selection across murine models of viral infection and autoimmune disease. Specifically, we recovered transcriptome and immune repertoire information for polyclonal T follicular helper cells following acute and chronic viral infection, CD8+ T cells with binding specificity restricted to two distinct peptides of lymphocytic choriomeningitis virus, and B and T cells isolated from the nervous system in the context of experimental autoimmune encephalomyelitis. We could relate repertoire features such as clonal expansion, germline gene usage, and clonal convergence to cell phenotypes spanning activation, memory, naive, antibody secretion, T cell inflation, and regulation. Together, this dataset provides a resource for experimental and computational immunologists that can be integrated with future single-cell immune repertoire and transcriptome sequencing datasets. Competing Interest Statement The authors have declared no competing interest.