scholarly journals The scaffold protein POSH regulates T lymphocyte function

2015 ◽  
Author(s):  
◽  
Cody A. Cunningham
Keyword(s):  
T Cell ◽  
Type I Diabetes ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
Scaffold Protein ◽  
Type I ◽  
Lymphocyte Function ◽  
Dependent Manner ◽  
Novel Target ◽  
Jnk Activation

T lymphocytes are critical mediators of the adaptive immune response. T cell receptor (TCR) mediated cJUN NH2-terminal kinase (JNK) activation is required for mounting proper T cell mediated immune responses. However, little is know as to how JNK activation is coupled to the TCR. This dissertation shows that the scaffold protein Plenty of SH3s (POSH) is required for optimal JNK activation and effector function in both CD4+ and CD8+ T cells. Additionally, this work shows that POSH is dispensable for JNK activation and positive and negative selection in developing thymocytes. Thus, POSH couples the TCR to JNK activation in a cell type and developmental stage dependent manner. This work also revels a novel target for the treatment of autoimmune disorders such as Type I Diabetes and Multiple Sclerosis.

Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes

Autoimmunity ◽  
1994 ◽  
Vol 18 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Susan Wong ◽  
Li Wen ◽  
Martin Hibberd ◽  
Ann Millward ◽  
Andrew Demaine
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Type I Diabetes ◽  
Cell Receptor ◽  
Type I ◽  
Newly Diagnosed

Long-Term Culture and T Cell Receptor Analysis of T Cell Clones Isolated from a Patient with Adenosine Deaminase Deficiency and Type I Diabetes

1994 ◽  
Vol 73 (3) ◽  
pp. 362-366 ◽  
Author(s):  
Piergiuseppe De Berardinis ◽  
Maria Neve Ombra ◽  
Catello Buono ◽  
Roberto Toraldo ◽  
Francesco Vetrano ◽  
...  
Keyword(s):  
T Cell ◽  
Adenosine Deaminase ◽  
T Cell Receptor ◽  
Type I Diabetes ◽  
Cell Receptor ◽  
Type I ◽  
Adenosine Deaminase Deficiency ◽  
T Cell Clones ◽  
Cell Clones

Defective T cell receptor/CD3 complex signaling in human type I diabetes

1994 ◽  
Vol 24 (4) ◽  
pp. 999-1002 ◽  
Author(s):  
Ruggero De Maria ◽  
Matilde Todaro ◽  
Giorgio Stassi ◽  
Francesco Di Blasi ◽  
Marco Giordano ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Type I Diabetes ◽  
Cell Receptor ◽  
Type I ◽  
Human Type ◽  
Complex Signaling

scholarly journals Genetic dissection of T cell receptor V beta gene requirements for spontaneous murine diabetes.

1991 ◽  
Vol 174 (3) ◽  
pp. 633-638 ◽  
Author(s):  
J A Shizuru ◽  
C Taylor-Edwards ◽  
A Livingstone ◽  
C G Fathman
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Autoimmune Diabetes ◽  
Type I Diabetes ◽  
Nod Mice ◽  
Cell Receptor ◽  
Type I ◽  
Genetic Dissection ◽  
Beta Gene

It has been demonstrated, in certain autoimmune disease models, that pathogenic T cells express antigen receptors of limited diversity. It has been suggested that the T cells responsible for the pathogenesis of type I diabetes mellitus might similarly demonstrate restricted T cell receptor (TCR) usage. Recently, attempts have been made to identify the V beta subset(s) that initiates and/or perpetuates the antiislet response in a mouse model of spontaneous autoimmune diabetes (non-obese diabetic [NOD] mice). In studies reported here, we have bred NOD mice to a mouse strain that congenitally lacks approximately one-half of the conventional TCR V beta alleles. Included in this deletion are TCR V beta gene products previously implicated as being involved in the pathogenesis of NOD disease. By studying second backcross-intercross animals, we were able to demonstrate that this deletion of TCR V beta gene segments did not prevent the development of insulitis or diabetes.

Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-κB transcription factors

2006 ◽  
Vol 8 (2) ◽  
pp. 154-161 ◽  
Author(s):  
June L Round ◽  
Lisa A Humphries ◽  
Tamar Tomassian ◽  
Paul Mittelstadt ◽  
Min Zhang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Scaffold Protein ◽  
P38 Kinase ◽  
Kinase Activation

scholarly journals Scaffold protein Disc large homolog 1 is required for T-cell receptor-induced activation of regulatory T-cell function

2012 ◽  
Vol 109 (5) ◽  
pp. 1625-1630 ◽  
Author(s):  
A. Zanin-Zhorov ◽  
J. Lin ◽  
J. Scher ◽  
S. Kumari ◽  
D. Blair ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Regulatory T Cell ◽  
Cell Function ◽  
Cell Receptor ◽  
Scaffold Protein ◽  
T Cell Function

scholarly journals T cell receptor recognition of hybrid insulin peptides bound to HLA-DQ8

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mai T. Tran ◽  
Pouya Faridi ◽  
Jia Jia Lim ◽  
Yi Tian Ting ◽  
Goodluck Onwukwe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Type I Diabetes ◽  
Binding Motif ◽  
Type I ◽  
Cell Repertoire ◽  
Islet Amyloid ◽  
Autoreactive T Cell ◽  
Β Chain

AbstractHLA-DQ8, a genetic risk factor in type I diabetes (T1D), presents hybrid insulin peptides (HIPs) to autoreactive CD4+ T cells. The abundance of spliced peptides binding to HLA-DQ8 and how they are subsequently recognised by the autoreactive T cell repertoire is unknown. Here we report, the HIP (GQVELGGGNAVEVLK), derived from splicing of insulin and islet amyloid polypeptides, generates a preferred peptide-binding motif for HLA-DQ8. HLA-DQ8-HIP tetramer+ T cells from the peripheral blood of a T1D patient are characterised by repeated TRBV5 usage, which matches the TCR bias of CD4+ T cells reactive to the HIP peptide isolated from the pancreatic islets of a patient with T1D. The crystal structure of three TRBV5+ TCR-HLA-DQ8-HIP complexes shows that the TRBV5-encoded TCR β-chain forms a common landing pad on the HLA-DQ8 molecule. The N- and C-termini of the HIP is recognised predominantly by the TCR α-chain and TCR β-chain, respectively, in all three TCR ternary complexes. Accordingly, TRBV5 + TCR recognition of HIP peptides might occur via a ‘polarised’ mechanism, whereby each chain within the αβTCR heterodimer recognises distinct origins of the spliced peptide presented by HLA-DQ8.

scholarly journals Molecular cloning of a novel human cDNA encoding a zinc finger protein that binds to the interleukin-3 promoter.

1994 ◽  
Vol 14 (8) ◽  
pp. 5099-5107 ◽  
Author(s):  
N Koyano-Nakagawa ◽  
J Nishida ◽  
D Baldwin ◽  
K Arai ◽  
T Yokota
Keyword(s):  
T Cell ◽  
Zinc Finger ◽  
Transcriptional Activity ◽  
Regulatory Region ◽  
Jurkat Cells ◽  
Type I ◽  
Dependent Manner ◽  
Cell Leukemia Virus Type ◽  
Transcription Activity ◽  
Interleukin 3

The CT/GC-rich region (-76 to -47) is one transcriptional regulatory region of the interleukin-3 (IL-3) gene which confers basic transcriptional activity and responds to trans-activation by human T-cell leukemia virus type I-encoded Tax. We isolated three types of cDNAs encoding Cys2/His2-type zinc finger proteins that bind to this region. Two were identical to known transcription factors, EGR1 and EGR2, and the other clone, named DB1, encoded a novel protein of 516 amino acids with six zinc finger motifs. DB1 mRNA was present in human tissues, ubiquitously. Two constitutive transcripts of 4.0 and 4.8 kb in length were present in Jurkat cells. Electrophoretic mobility shift assay, with specific antibodies, showed that DB1 constitutively binds to this region whereas EGR1 binds in a T-cell activation-dependent manner. Overexpression of DB1 in Jurkat cells had no detectable effect on the transcription activity of the IL-3 promoter, in a transient-transfection assay. EGR1 and EGR2 increased IL-3 promoter activity when the transfected cells were stimulated with phorbol-12-myristate-13-acetate and A23187. When DB1 was cotransfected with a Tax expression vector, transcription activity of the IL-3 promoter induced by Tax was significantly increased, while EGR1 and EGR2 were without effect. These results suggest that EGR1 has a role in inducible transcription of the IL-3 gene, while DB1 sustains basal transcriptional activity and also cooperates with Tax to activate the IL-3 promoter.

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