Salmonid IGH genes: From genomics to repertoire sequencing

2019 ◽  
Vol 91 ◽  
pp. 434-435
Author(s):  
Susana Magadan ◽  
Aleksei Krasnov ◽  
Saida Hadi-Saljoki ◽  
Rosario Castro ◽  
Irene Salinas ◽  
...  
Keyword(s):  
Igh Genes ◽  
Repertoire Sequencing

scholarly journals Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linling He ◽  
Anshul Chaudhary ◽  
Xiaohe Lin ◽  
Cindy Sou ◽  
Tanwee Alkutkar ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Heptad Repeat ◽  
T Cell Epitopes ◽  
Vaccine Strategy ◽  
Cell Responses ◽  
Self Assembling ◽  
Protein Nanoparticles ◽  
Main Target ◽  
Repertoire Sequencing

AbstractEbola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1C modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1C exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display.

scholarly journals Massive clonal expansion of polycytotoxic skin and blood CD8+ T cells in patients with toxic epidermal necrolysis

2021 ◽  
Vol 7 (12) ◽  
pp. eabe0013
Author(s):  
Axel Patrice Villani ◽  
Aurore Rozieres ◽  
Benoît Bensaid ◽  
Klara Kristin Eriksson ◽  
Amandine Mosnier ◽  
...  
Keyword(s):  
T Cells ◽  
Toxic Epidermal Necrolysis ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
Effector Memory ◽  
Skin Symptoms ◽  
Tcr Repertoire ◽  
Repertoire Sequencing ◽  
Life Threatening ◽  
Cutaneous Adverse Drug Reaction

Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous adverse drug reaction. To better understand why skin symptoms are so severe, we conducted a prospective immunophenotyping study on skin and blood. Mass cytometry results confirmed that effector memory polycytotoxic CD8+ T cells (CTLs) are the main leucocytes in TEN blisters at the acute phase. Deep T cell receptor (TCR) repertoire sequencing identified massive expansion of unique CDR3 clonotypes in blister cells. The same clones were highly expanded in patient’s blood, and the degree of their expansion showed significant correlation with disease severity. By transducing α and β chains of the expanded clonotypes into a TCR-defective cell line, we confirmed that those cells were drug specific. Collectively, these results suggest that the relative clonal expansion and phenotype of skin-recruited CTLs condition the clinical presentation of cutaneous adverse drug reactions.

scholarly journals Use of immune repertoire sequencing to resolve discordant microscopic and immunochemical findings in a case of T cell-rich large B cell lymphoma in a young dog

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Gary Kwok Cheong Lee ◽  
Dorothee Bienzle ◽  
Stefan Matthias Keller ◽  
Mei-Hua Hwang ◽  
Nikos Darzentas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Repertoire ◽  
Large B Cell Lymphoma ◽  
Repertoire Sequencing ◽  
Reactive Lymphocytes ◽  
Large B Cell

Abstract Background Lymphocytic neoplasms with frequent reactive lymphocytes are uncommonly reported in dogs, and can pose a diagnostic challenge. Different diagnostic modalities such as cytology, flow cytometry, histopathology, immunohistochemistry, and clonality testing, are sometimes required for a diagnosis. This report illustrates the value of using a multi-modal diagnostic approach to decipher a complex lymphocytic tumor, and introduces immune repertoire sequencing as a diagnostic adjunct. Case presentation A 10-month-old Great Dane was referred for marked ascites. Cytologic analysis of abdominal fluid and hepatic aspirates revealed a mixed lymphocyte population including numerous large lymphocytes, yielding a diagnosis of lymphoma. Flow cytometrically, abdominal fluid lymphocytes were highly positive for CD4, CD5, CD18, CD45, and MHC II, consistent with T cell lymphoma. Due to a rapidly deteriorating clinical condition, the dog was euthanized. Post mortem histologic evaluation showed effacement of the liver by aggregates of B cells surrounded by T cells, suggestive of hepatic T cell-rich large B cell lymphoma. Immune repertoire sequencing confirmed the presence of clonal B cells in the liver but not the abdominal fluid, whereas reactive T cells with shared, polyclonal immune repertoires were found in both locations. Conclusions T cell-rich large B cell lymphoma is a rare neoplasm in dogs that may be challenging to diagnose and classify due to mixed lymphocyte populations. In this case, the results of histopathology, immunohistochemistry and immune repertoire sequencing were most consistent with a hepatic B cell neoplasm and reactive T cells exfoliating into the abdominal fluid. Immune repertoire sequencing was helpful in delineating neoplastic from reactive lymphocytes and characterizing repertoire overlap in both compartments. The potential pitfalls of equating atypical cytomorphology and monotypic marker expression in neoplasia are highlighted.

Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2337-2342 ◽  
Author(s):  
Paolo Ghia ◽  
Giuseppina Prato ◽  
Cristina Scielzo ◽  
Stefania Stella ◽  
Massimo Geuna ◽  
...  
Keyword(s):  
B Cell ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
Pcr Analysis ◽  
Cell Repertoire ◽  
Healthy Elderly ◽  
B Cell Repertoire ◽  
Igh Genes

Abstract The responsiveness and diversity of peripheral B-cell repertoire decreases with age, possibly because of B-cell clonal expansions, as suggested by the incidence of serum monoclonal immunoglobulins and of monoclonal chronic lymphocytic leukemia (CLL)–like B lymphocytes in clinically silent adults. We phenotyped peripheral blood cells from 500 healthy subjects older than 65 years with no history or suspicion of malignancies and no evidence of lymphocytosis. In 19 cases (3.8%) a κ/λ ratio of more than 3:1 or less than 1:3 was found: 9 were CD5+, CD19+, CD23+, CD20low, CD79blow, sIglow (classic CLL-like phenotype); 3 were CD5+, CD19+, CD23+, CD20high, CD79blow, sIglow (atypical CLL-like), and 7 were CD5-, CD19+, CD20high, CD23-, CD79bbright, FMC7+, sIgbright (non–CLL-like). In 2 subjects, 2 phenotypically distinct unrelated clones were concomitantly evident. No cases were CD10+. Polymerase chain reaction (PCR) analysis demonstrated a monoclonal rearrangement of IgH genes in 15 of 19 cases. No bcl-1 or bcl-2 rearrangements were detected. Using a gating strategy based on CD20/CD5/CD79 expression, 13 additional CLL-like B-cell clones were identified (cumulative frequency of classic CLL-like: 5.5%). Thus, phenotypically heterogeneous monoclonal B-lymphocyte expansions are common among healthy elderly individuals and are not limited to classic CLL-like clones but may have the phenotypic features of different chronic lymphoproliferative disorders, involving also CD5- B cells.

A primer set for comprehensive amplification of V-genes from rhesus macaque origin based on repertoire sequencing

2019 ◽  
Vol 465 ◽  
pp. 67-71 ◽  
Author(s):  
Ronit Rosenfeld ◽  
Anat Zvi ◽  
Eitan Winter ◽  
Ronen Hope ◽  
Ofir Israeli ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
V Genes ◽  
Repertoire Sequencing

scholarly journals Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
William S DeWitt ◽  
Anajane Smith ◽  
Gary Schoch ◽  
John A Hansen ◽  
Frederick A Matsen ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Genetic Background ◽  
Cell Receptor ◽  
Sequencing Data ◽  
Human T Cell ◽  
Disease Associations ◽  
Repertoire Sequencing ◽  
Mhc Polymorphism ◽  
Occurrence Patterns

The T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturbation induced by a given immunological challenge is conditioned on genetic background via major histocompatibility complex (MHC) polymorphism. We explore associations between MHC alleles, immune exposures, and shared TCRs in a large human cohort. Using a previously published repertoire sequencing dataset augmented with high-resolution MHC genotyping, our analysis reveals rich structure: striking imprints of common pathogens, clusters of co-occurring TCRs that may represent markers of shared immune exposures, and substantial variations in TCR-MHC association strength across MHC loci. Guided by atomic contacts in solved TCR:peptide-MHC structures, we identify sequence covariation between TCR and MHC. These insights and our analysis framework lay the groundwork for further explorations into TCR diversity.

scholarly journals Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1101-1107 ◽  
Author(s):  
AJ Furley ◽  
BR Reeves ◽  
S Mizutani ◽  
LJ Altass ◽  
SM Watt ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Myeloid Cell ◽  
Cell Receptor ◽  
High Level Expression ◽  
Igh Genes ◽  
T Cell Receptor Beta ◽  
Molecular Phenotypes ◽  
High Level ◽  
Receptor Beta

The cell line KG1 derived from a patient with erythroleukemia in myeloblastic relapse has the composite phenotype and functional repertoire of myeloblasts. In marked contrast, its subline KG1a has lost myeloid features, acquired new karyotypic markers, and has three characteristics associated with immature T cells: low-level expression of the T cell receptor beta mRNA (but not alpha) transcribed from a germline gene; high-level expression of T3 delta mRNA and intracellular, but not cell surface, T3 protein; and expression of the CD7/gp40 T cell-associated membrane antigen. Both KG1 and KG1a transcribe unrearranged IgH genes. These data suggest that either the KG1 cell line was derived from a common myeloid-lymphoid progenitor or that the KG1a subline phenotype is aberrant.

scholarly journals Deep learning identifies antigenic determinants of severe SARS-CoV-2 infection within T-cell repertoires

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John-William Sidhom ◽  
Alexander S. Baras
Keyword(s):  
Deep Learning ◽  
T Cell ◽  
Clinical Outcomes ◽  
Clinical Course ◽  
Severity Of Illness ◽  
Severe Infection ◽  
Cell Receptor ◽  
Asymptomatic Infection ◽  
Antigenic Determinants ◽  
Repertoire Sequencing

AbstractSARS-CoV-2 infection is characterized by a highly variable clinical course with patients experiencing asymptomatic infection all the way to requiring critical care support. This variation in clinical course has led physicians and scientists to study factors that may predispose certain individuals to more severe clinical presentations in hopes of either identifying these individuals early in their illness or improving their medical management. We sought to understand immunogenomic differences that may result in varied clinical outcomes through analysis of T-cell receptor sequencing (TCR-Seq) data in the open access ImmuneCODE database. We identified two cohorts within the database that had clinical outcomes data reflecting severity of illness and utilized DeepTCR, a multiple-instance deep learning repertoire classifier, to predict patients with severe SARS-CoV-2 infection from their repertoire sequencing. We demonstrate that patients with severe infection have repertoires with higher T-cell responses associated with SARS-CoV-2 epitopes and identify the epitopes that result in these responses. Our results provide evidence that the highly variable clinical course seen in SARS-CoV-2 infection is associated to certain antigen-specific responses.

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