scholarly journals Nomenclature for T cell receptor (TCR) gene segments of the immune system

2008 ◽  
Vol 94 (2) ◽  
pp. 391-392
Author(s):  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor

Approach to primary immunodeficiency

2019 ◽  
Vol 40 (6) ◽  
pp. 465-469 ◽  
Author(s):  
Ashley L. Devonshire ◽  
Melanie Makhija
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Primary Immunodeficiency ◽  
Cell Receptor ◽  
Antibody Deficiency ◽  
Haemophilus Influenzae Type ◽  
Toll Like Receptor ◽  
T Cell Lymphopenia ◽  
Excision Circles

Primary immunodeficiency diseases are inherited defects of the innate or adaptive arms of the immune system that lead to an increase in the incidence, frequency, or severity of infections and/or immune dysregulation. There may be defects in the adaptive arm of the immune system, including combined immunodeficiencies and antibody deficiency syndromes, or abnormalities in innate immunity, such as defects of phagocytes, the complement pathway, or toll-like receptor mediated signaling. Recurrent sinopulmonary infections with encapsulated bacteria such as Haemophilus influenzae type B or Streptococcus pneumoniae may be characteristic of an antibody deficiency syndrome. Frequent viral, fungal, or protozoal infections may suggest T lymphocyte impairment. Multiple Staphylococcus skin infections and fungal infections may imply neutrophil dysfunction or the Hyper-IgE syndrome, and recurrent Neisseria infection is a characteristic manifestation of late complement component (C5‐9, or the membrane attack complex) defects. Recurrent viral or pyogenic bacterial infections, often without the presence of a significant inflammatory response, suggest a defect in toll-like receptor signaling. Mycobacterial infections are characteristic of defects in the interleukin (IL) 12/interferon γ pathway. Screening of newborns for T-cell lymphopenia by using polymerase chain reaction to amplify T-cell receptor excision circles, which are formed when a T cell rearranges the variable region of its receptor, serves as a surrogate for newly synthesized naive T cells. Because of very low numbers of T-cell receptor excision circles, severe combined immunodeficiency, 22q11.2 syndrome, and other causes of T-cell lymphopenia have been identified in newborns.

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 Predictable αβ T-Cell Receptor Selection toward an HLA-B*3501-Restricted Human Cytomegalovirus Epitope

2007 ◽  
Vol 81 (13) ◽  
pp. 7269-7273 ◽  
Author(s):  
Rebekah M. Brennan ◽  
John J. Miles ◽  
Sharon L. Silins ◽  
Melissa J. Bell ◽  
Jacqueline M. Burrows ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Human Cytomegalovirus ◽  
Clinical Immunology ◽  
Cell Receptor ◽  
Cell Populations ◽  
Tcr Repertoire ◽  
Pp65 Antigen

ABSTRACT Human cytomegalovirus (HCMV) elicits a very large burden on the immune system, with approximately one in ten T cells being reserved solely to manage this infection. However, information on the clonotypic composition of these vast T-cell populations is limited. In this study, we sequenced 116 T-cell receptor (TcR) α/β-chains specific for the highly immunogenic HLA-B*3501-resticted epitope IPSINVHHY from the pp65 antigen. Interestingly, T cells recovered from all donors bore an identical or near-identical TRBV28/TRBJ1-4/TRAV17/TRAJ33 TcR. The ability to predict the responding αβ TcR repertoire before viral infection should prove a powerful tool for basic and clinical immunology.

scholarly journals T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Asaf Madi ◽  
Asaf Poran ◽  
Eric Shifrut ◽  
Shlomit Reich-Zeliger ◽  
Erez Greenstein ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Sequence Similarity ◽  
Cell Receptor ◽  
Immune Checkpoint Blockade ◽  
Sequencing Data ◽  
Cell Repertoire ◽  
Similarity Networks ◽  
Sequence Similarity Networks

Diversity of T cell receptor (TCR) repertoires, generated by somatic DNA rearrangements, is central to immune system function. However, the level of sequence similarity of TCR repertoires within and between species has not been characterized. Using network analysis of high-throughput TCR sequencing data, we found that abundant CDR3-TCRβ sequences were clustered within networks generated by sequence similarity. We discovered a substantial number of public CDR3-TCRβ segments that were identical in mice and humans. These conserved public sequences were central within TCR sequence-similarity networks. Annotated TCR sequences, previously associated with self-specificities such as autoimmunity and cancer, were linked to network clusters. Mechanistically, CDR3 networks were promoted by MHC-mediated selection, and were reduced following immunization, immune checkpoint blockade or aging. Our findings provide a new view of T cell repertoire organization and physiology, and suggest that the immune system distributes its TCR sequences unevenly, attending to specific foci of reactivity.

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