scholarly journals First patient in the Iranian Registry with novel DOCK2 gene mutation, presenting with skeletal tuberculosis, and review of literature

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Niusha Sharifinejad ◽  
Homa Sadri ◽  
Arash Kalantari ◽  
Samaneh Delavari ◽  
Amirhosein Noohi ◽  
...  
Keyword(s):  
T Cell ◽  
Early Onset ◽  
Screening Program ◽  
Human Herpesvirus ◽  
Cell Receptor ◽  
Recurrent Pneumonia ◽  
Skeletal Tuberculosis ◽  
Humoral Immune ◽  
Trec Assay ◽  
High Level

Abstract Background Dedicator of cytokinesis 2 (DOCK2) deficiency is an inborn error of immunity characterized by cellular and humoral immunological abnormalities leading to early-onset infections. Case presentation We reported a novel case of a 27 months old girl presenting with recurrent pneumonia and a history of skeletal tuberculosis at the age of 19-month-old. Her immunological workup revealed persistent lymphopenia and low CD4 + T cell count along with elevated levels of CD19 +, CD20 +, CD16 +, and CD56 + cells. Furthermore, she had a high level of immunoglobulin (Ig) E and a slightly reduced IgM level with a non-protective antibody titer against diphtheria. The whole-exome sequencing (WES) analysis identified a homozygous frameshift deletion mutation (c.1512delG, p.I505Sfs*28) in exon 16 of the DOCK2 gene. We also conducted electronic searches in PubMed, Web of Science, and Scopus databases and reviewed the articles reporting patients with DOCK2 deficiency. The literature search yielded 14 DOCK2-deficient patients suffering from both cellular and humoral immune defects leading to early-onset infections, particularly human herpesvirus (HHV) infection. Conclusion DOCK2 deficiency should be considered in the context of severe or unusual early-onset infections, especially HHV infections, in a patient with a probable clinical diagnosis of combined immunodeficiency. We also recommended that DOCK2-deficient patients might benefit from T-cell receptor excision circle (TREC) assay as part of the routine newborn screening program.

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.

Athymic mice express a high level of functional γ-chain but greatly reduced levels of α- and β-chain T-cell receptor messages

Nature ◽  
1986 ◽  
Vol 324 (6096) ◽  
pp. 482-485 ◽  
Author(s):  
Yasunobu Yoshikai ◽  
Marciano D. Reis ◽  
Tak W. Mak
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Athymic Mice ◽  
High Level ◽  
Β Chain

scholarly journals The U24 Protein from Human Herpesvirus 6 and 7 Affects Endocytic Recycling

2009 ◽  
Vol 84 (3) ◽  
pp. 1265-1275 ◽  
Author(s):  
Brian M. Sullivan ◽  
Laurent Coscoy
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Human Herpesvirus ◽  
Cell Receptor ◽  
Receptor Expression ◽  
Membrane Insertion ◽  
Human Herpesvirus 6 ◽  
Endosomal Recycling ◽  
Endosomal Transport ◽  
Basic Cellular Process

ABSTRACT Modulation of T-cell receptor expression and signaling is essential to the survival of many viruses. The U24 protein expressed by human herpesvirus 6A, a ubiquitous human pathogen, has been previously shown to downregulate the T-cell receptor. Here, we show that U24 also mediates cell surface downregulation of a canonical early endosomal recycling receptor, the transferrin receptor, indicating that this viral protein acts by blocking early endosomal recycling. We present evidence that U24 is a C-tail-anchored protein that is dependent for its function on TRC40/Asna-1, a component of a posttranslational membrane insertion pathway. Finally, we find that U24 proteins from other roseoloviruses have a similar genetic organization and a conserved function that is dependent on a proline-rich motif. Inhibition of a basic cellular process by U24 has interesting implications not only for the pathogenicity of roseoloviruses but also for our understanding of the biology of endosomal transport.

scholarly journals Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules.

1989 ◽  
Vol 169 (3) ◽  
pp. 795-806 ◽  
Author(s):  
H S Teh ◽  
H Kishi ◽  
B Scott ◽  
H Von Boehmer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Large Fraction ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Male Transgenic Mouse ◽  
Low Levels ◽  
High Level

Transgenic mice that carry on a large fraction of their T cells an alpha/beta T cell receptor that recognizes the male antigen in the context of H-2Db molecules were constructed. An mAb specific for the transgenic receptor was developed and used to analyze T cell subsets in male transgenic H-2b mice. The vast majority of immature CD4+8+ T cells that express the transgenic TCR were deleted in the male transgenic mouse. Nevertheless, the majority of T cells spared by this deletion process expressed a high level of the transgenic TCR. These T cells, however, had an abnormal CD4/CD8 phenotype in that they expressed either no CD8 molecules or only low levels.

scholarly journals Downregulation of the T-Cell Receptor Complex and Impairment of T-Cell Activation by Human Herpesvirus 6 U24 Protein

2007 ◽  
Vol 82 (2) ◽  
pp. 602-608 ◽  
Author(s):  
Brian M. Sullivan ◽  
Laurent Coscoy
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Herpesvirus ◽  
Cell Receptor ◽  
Immune Recognition ◽  
Human Herpesvirus 6 ◽  
Herpesvirus 6

ABSTRACT We have performed a screen aimed at identifying human herpesvirus 6 (HHV-6)-encoded proteins that modulate immune recognition. Here we show that the U24 protein encoded by HHV-6 variant A downregulates cell surface expression of the T-cell receptor (TCR)/CD3 complex, a complex essential to T-cell activation and the generation of an immune adaptive response. In the presence of U24, the TCR/CD3 complex is endocytosed but is not recycled back to the plasma membrane. Instead, it accumulates in early and late endosomes. Interestingly, whereas CD3 downregulation from the cell surface is normally associated with T-cell activation, U24 downregulates CD3 independently of T-cell activation. Moreover, we found that U24-expressing T cells are resistant to activation by antigen-presenting cells. HHV-6 has evolved a unique mechanism of inhibition of T-cell activation that may impair the establishment of an adaptive immune response. Furthermore, lymphocyte activation creates an environment favorable to the reactivation and replication of lymphotropic herpesviruses. Thus, by inhibiting T-cell activation, HHV-6 might limit its reactivation and thus minimize immune recognition.

scholarly journals Antigen experience relaxes the organisational structure of the T cell receptor repertoire

2021 ◽  
Author(s):  
Michal Mark ◽  
Shlomit Reich-Zeliger ◽  
Erez Greenstein ◽  
Dan Reshef ◽  
Asaf Madi ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Receptor Repertoire ◽  
Adult Mice ◽  
High Level ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

The creation and evolution of the T cell receptor repertoire within an individual combines stochastic and deterministic processes. We systematically examine the structure of the repertoire in different T cell subsets in young, adult and LCMV infected mice, from the perspective of variable gene usage, nucleotide sequences and amino acid motifs. Young individuals share a high level of organization, especially in the frequency distribution of variable genes and amino acid motifs. In adult mice, this structure relaxes and is replaced by idiotypic evolution of the effector and regulatory repertoire. The repertoire of CD4+ regulatory T cells was more similar to naïve cells in young mice, but became more similar to effectors with age. Finally, we observed a dramatic restructuring of the repertoire following infection with LCMV. We hypothesize that the stochastic process of recombination and thymic selection initially impose a strong structure to the repertoire, which gradually relaxes following asynchronous responses to different antigens during life.

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

Abstract 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 Staphylococcal Enterotoxin-Like Toxins U2 and V, Two New Staphylococcal Superantigens Arising from Recombination within the Enterotoxin Gene Cluster

2006 ◽  
Vol 74 (8) ◽  
pp. 4724-4734 ◽  
Author(s):  
Damien Yann Thomas ◽  
Sophie Jarraud ◽  
Brigitte Lemercier ◽  
Gregoire Cozon ◽  
Klara Echasserieau ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Cluster ◽  
T Cell Receptor ◽  
Insertion Sequence ◽  
Cell Receptor ◽  
Enterotoxin Gene ◽  
Enterotoxin Genes ◽  
High Prevalence ◽  
High Level ◽  
T Cell Receptor Vβ

ABSTRACT To test the hypothesis that the Staphylococcus aureus enterotoxin gene cluster (egc) can generate new enterotoxin genes by recombination, we analyzed the egc locus in a broad panel of 666 clinical isolates of S. aureus. egc was present in 63% of isolates, confirming its high prevalence. The archetypal organization of the egc locus, consisting of five enterotoxin genes plus two pseudogenes, was found in 409 of 421 egc-positive strains. The egc locus was incomplete in a few strains and occasionally harbored an insertion sequence and transposase genes. These strains may represent evolutionary intermediates of the egc locus. One strain with an atypical egc locus produced two new enterotoxins, designated SElV and SElU2, generated by (i) recombination between selm and sei, producing selv, and (ii) a limited deletion in the φent1-φent2 pseudogenes, producing selu2. Recombinant SElV and SElU2 had superantigen activity, as they specifically activated the T-cell families Vβ 6, Vβ 18, and Vβ 21 (SElV) and Vβ 13.2 and Vβ 14 (SElU2). Immunoscope analysis showed a Gaussian CDR3 size distribution of T-cell receptor Vβ chain junctional transcripts of expanded Vβ subsets in toxin-stimulated cultures, reflecting a high level of polyclonality. These data show that egc is indeed capable of generating new superantigen genes through recombination.

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