Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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ScRNAseq of HLA-A*02:01-G5R18-26-specifi CD8+ T cells

ABSTRACT: In 2022, a global mpox outbreak occurred, and remains a concern today. The T cell memory response to MPXV infection has not been fully investigated. In this study, we evaluated this response in convalescent and MVA-BN vaccinated individuals using VACV-infected cells. Detailed phenotypic and scRNAseq analysis was focused on the immunodominant HLA-A*02:01-G5R18-26-specific CD8+ T cell response. T cells from convalescent individuals showed greater cytotoxicity, migratory potential to site of infection and TCR clonal expansion. Our study suggests a better functional profile of MPXV-specific memory T cells induced by natural infection, which may have an implication on the long-term protective responses to future infection.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER:

PROVIDER: E-MTAB-14244 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): ERP162162

REPOSITORIES: biostudies-arrayexpress

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Project description:Memory B cells represent one of the pillar of humoral protection and are found in the circulation and secondary lymphoid organs several decades after initial pathogen or vaccine encounter. The exact cellular and biological mechanisms allowing long-term survival of quiescent cells in such a fluctuating microenvironment remain poorly understood. Assessing the true longevity of human memory B cells against common pathogens is, in most settings, hindered by the possibility for any given individual to re-encounter them during his lifetime. Smallpox, officially declared eradicated in 1980 (Fenner WHO 1988), represents one notable exception. Alongside smallpox eradication, anti-smallpox vaccination, based on the live Vaccinia virus, was progressively discontinued during the 1970s. As such, any detectable anti-vaccinia memory B cell in an individual post 2010 would likely have been generated more than 40 years ago, without any re-stimulation with the immunizing antigen during that timeframe. Anti-vaccinia antibodies serum titers remain stable in human for more than 80 years after first vaccination (Amanna NEJM 2007, PMID: 17989383), with several identified immunodominant epitopes including the envelope glycoprotein B5R (Lantto J Virol 2011, PMID: 21147924). Anti-vaccinia memory B cells have similarly been followed longitudinally in the blood for up to 65 years post vaccination (Amanna NEJM 2007, PMID: 17989383 ; Crotty JI 2003, PMID : 14607890) and, following a contraction phase taking place in the first couple of years after immunization, reach a remarkably stable plateau that last for decades at around 0.1% of total circulating IgG+ memory B cells. Functional analysis of such long-lived memory B cells, however, is still lacking. As a proxy to study long-lived memory B cells, IgG+ switched memory B cells specific for the immunodominant Vaccinia antigen B5R (B5R+ IgG+ memory B cells) were sorted and analyzed by scRNAseq from the spleen of six organ donors, collected between 2015 and 2018. For all donors, B5R+ IgG+ memory B cells were sorted alongside total IgG+ memory B cells (live IgD-CD27+IgG+CD20+CD3-CD14-CD16-) and naïve B cells (live IgD+CD27-CD38-CD24-CD20+CD3-CD14-CD16-). Single-cell mRNA sequencing was performed according to an adapted version of the SORT-seq protocol (Muraro et al., 2016, PMID: 27693023), with cDNA libraries generation, sequencing and reads alignment performed at Single Cell Discoveries (Utrecht, Netherlands).

Project description:Leptospirosis is the most widespread zoonotic disease in the world. The lack of an adequate laboratory test is a major barrier for the diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease. In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response against leptospiral antigens from 274 individuals, including 80 acute-, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results. We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL and Loa22 are already known to be recognized by sera from human patients, thus serving as a proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients. Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the accuracy of these antigens in more appropriate diagnostic platforms. Antibody profiling was peformed on sera from infected and non-infected subjects to investigate the IgG response against leptospiral antigens. These samples comprised 80 acute-, 80 convalescent-phase patients and 114 healthy control subjects, including 29 subjects from United States (non-endemic area), 35 blood donors from Salvador/Brazil (endemic area) and 50 healthy individuals from region with high endemicity of leptospirosis.

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ScRNAseq of HLA-A*02:01-G5R18-26-specifi CD8+ T cells

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