scholarly journals The Evolution of Rag Gene Enhancers and Transcription Factor E and Id Proteins in the Adaptive Immune System

2021 ◽  
Vol 22 (11) ◽  
pp. 5888
Author(s):  
Genki Yoshikawa ◽  
Kazuko Miyazaki ◽  
Hiroyuki Ogata ◽  
Masaki Miyazaki
Keyword(s):  
Immune System ◽  
Dna Recombination ◽  
Regulatory System ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Regulatory Elements ◽  
Adaptive Immune ◽  
Helix Loop Helix ◽  
Rag Genes ◽  
Rag 1

Adaptive immunity relies on the V(D)J DNA recombination of immunoglobulin (Ig) and T cell receptor (TCR) genes, which enables the recognition of highly diverse antigens and the elicitation of antigen-specific immune responses. This process is mediated by recombination-activating gene (Rag) 1 and Rag2 (Rag1/2), whose expression is strictly controlled in a cell type-specific manner; the expression of Rag1/2 genes represents a hallmark of lymphoid lineage commitment. Although Rag genes are known to be evolutionally conserved among jawed vertebrates, how Rag genes are regulated by lineage-specific transcription factors (TFs) and how their regulatory system evolved among vertebrates have not been fully elucidated. Here, we reviewed the current body of knowledge concerning the cis-regulatory elements (CREs) of Rag genes and the evolution of the basic helix-loop-helix TF E protein regulating Rag gene CREs, as well as the evolution of the antagonist of this protein, the Id protein. This may help to understand how the adaptive immune system develops along with the evolution of responsible TFs and enhancers.

Reduction Of Immune Repertoire Diversity Through DNA Sequence Constraints At VDJ Junctions

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4944-4944
Author(s):  
Bryan Howie ◽  
Harlan Robins ◽  
Christopher S Carlson
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Immune Repertoire ◽  
Adaptive Immune ◽  
Repertoire Diversity ◽  
Equity Ownership ◽  
Junctional Diversity

Abstract B and T lymphocytes are effector cells of the adaptive immune system. These cells express surface receptors that bind a huge variety of antigens, and together they comprise a person’s immune repertoire. A diverse repertoire is essential for mounting robust immune responses against a wide range of pathogens, and repertoire diversity affects the probability that DNA sequencing can uniquely tag a clonally expanded population of cells for the detection of minimum residual disease (MRD) during cancer treatment. Immune repertoire diversity arises partly through the combinatorial splicing of gene segments from the variable (V), diversity (D), and joining (J) regions of a B or T cell receptor locus. Much additional diversity is created through the stochastic insertion and deletion of nucleotides at the splice junctions, and by somatic hypermutation (SHM) in maturing lymphocytes. The generation of junctional diversity is an important part of this process, but it may be constrained by the underlying biological mechanisms. To explore the landscape of junctional diversity among immune receptor loci, we developed a likelihood model that can annotate VDJ junctions in the presence of SHM and compute the probability that a given receptor sequence was generated only once in a person’s repertoire, which is essential for tracking MRD. Using high-throughput sequencing data from several individuals and a range of receptor loci, we identify mechanistic constraints that limit B and T cell receptor diversity. For example, we show that the usual variability in CDR3 length is reduced at the immunoglobulin kappa (IgK) locus, and we connect this finding to sequence motifs that constrain nucleotide deletion at the ends of IgK gene segments. Our findings will inform future genetic studies of the adaptive immune system, and they provide quantitative guidance for deciding which cancer clones can be tracked for reliable MRD detection. Disclosures: Howie: Adaptive Biotechnologies: Employment, Equity Ownership. Robins:Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties. Carlson:Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties.

scholarly journals Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4099-4107 ◽  
Author(s):  
Harlan S. Robins ◽  
Paulo V. Campregher ◽  
Santosh K. Srivastava ◽  
Abigail Wacher ◽  
Cameron J. Turtle ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Dna Sequencing ◽  
T Cell Receptor ◽  
Hematopoietic Cell Transplantation ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Adaptive Immune ◽  
Αβ T Cells

Abstract The adaptive immune system uses several strategies to generate a repertoire of T- and B-cell antigen receptors with sufficient diversity to recognize the universe of potential pathogens. In αβ T cells, which primarily recognize peptide antigens presented by major histocompatibility complex molecules, most of this receptor diversity is contained within the third complementarity-determining region (CDR3) of the T-cell receptor (TCR) α and β chains. Although it has been estimated that the adaptive immune system can generate up to 1016 distinct αβ pairs, direct assessment of TCR CDR3 diversity has not proved amenable to standard capillary electrophoresis-based DNA sequencing. We developed a novel experimental and computational approach to measure TCR CDR3 diversity based on single-molecule DNA sequencing, and used this approach to determine the CDR3 sequence in millions of rearranged TCRβ genes from T cells of 2 adults. We find that total TCRβ receptor diversity is at least 4-fold higher than previous estimates, and the diversity in the subset of CD45RO+ antigen-experienced αβ T cells is at least 10-fold higher than previous estimates. These methods should prove valuable for assessment of αβ T-cell repertoire diversity after hematopoietic cell transplantation, in states of congenital or acquired immunodeficiency, and during normal aging.

Evolution and age characteristics of the innate and adaptive immune system

2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune

scholarly journals Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System

2021 ◽  
Vol 8 (8) ◽  
pp. 2004979
Author(s):  
Jun‐Young Park ◽  
Sung Jean Park ◽  
Jun Young Park ◽  
Sang‐Hyun Kim ◽  
Song Kwon ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Protein Corona ◽  
Unfolded Protein ◽  
Adaptive Immune

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Programming Native CRISPR Arrays for the Generation of Targeted Immunity

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Alexander P. Hynes ◽  
Simon J. Labrie ◽  
Sylvain Moineau
Keyword(s):  
Immune System ◽  
Nucleic Acid ◽  
Genome Editing ◽  
Dna Sequence ◽  
Adaptive Immune System ◽  
Natural Process ◽  
The Public ◽  
Adaptive Immune ◽  
Public Consciousness ◽  
Industrial Settings

ABSTRACT The adaptive immune system of prokaryotes, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes), results in specific cleavage of invading nucleic acid sequences recognized by the cell’s “memory” of past encounters. Here, we exploited the properties of native CRISPR-Cas systems to program the natural “memorization” process, efficiently generating immunity not only to a bacteriophage or plasmid but to any specifically chosen DNA sequence. IMPORTANCE CRISPR-Cas systems have entered the public consciousness as genome editing tools due to their readily programmable nature. In industrial settings, natural CRISPR-Cas immunity is already exploited to generate strains resistant to potentially disruptive viruses. However, the natural process by which bacteria acquire new target specificities (adaptation) is difficult to study and manipulate. The target against which immunity is conferred is selected stochastically. By biasing the immunization process, we offer a means to generate customized immunity, as well as provide a new tool to study adaptation.

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