scholarly journals Regulation of the Stability of Heat-Stable Antigen mRNA by Interplay between Two Novel cis Elements in the 3′ Untranslated Region

1998 ◽  
Vol 18 (2) ◽  
pp. 815-826 ◽  
Author(s):  
Qunmin Zhou ◽  
Yong Guo ◽  
Yang Liu
Keyword(s):  
T Cell Activation ◽  
Untranslated Region ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Rna Stability ◽  
Rna Degradation ◽  
Reading Frame ◽  
Heat Stable ◽  
Heat Stable Antigen ◽  
The Stability

ABSTRACT The heat-stable antigen (HSA) is a costimulatory molecule for T-cell activation. Its expression is strictly regulated during lymphocyte development and differentiation. Recent studies using HSA-transgenic mice have demonstrated that this regulated expression is critical for normal development of T and B lymphocytes. However, the mechanisms that control the expression of HSA are largely unknown. HSA mRNA is comprised of a 0.23-kb open reading frame and a 1.5-kb 3′ untranslated region (3′UTR). The function of the long 3′UTR has not been addressed. Here we investigate the role of the 3′UTR of HSA mRNA. We show that a 160-bp element, located in the region of nucleotides 1465 to 1625 in the 3′UTR of HSA mRNA, promotes RNA degradation and that this effect is neutralized by a 43-bp fragment approximately 1 kb upstream of the negative cis element. Both positive and negative cis elements in the HSA mRNA are distinct from other sequences that are known to modulate mRNA stability. These results provide direct evidence that the interplay between two novelcis elements in the 3′UTR of HSA mRNA determines cell surface HSA expression by modulating its RNA stability.

Heat-stable antigen is expressed by murine keratinocytes and delivers costimulatory signals in T-cell activation

1995 ◽  
Vol 4 (5) ◽  
pp. 291-296 ◽  
Author(s):  
Gabicla Erdmann ◽  
Joachim Saloga ◽  
Mansour Mohamadzadeh ◽  
Detlef Becker ◽  
Jurgen Knop ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Heat Stable ◽  
Heat Stable Antigen ◽  
Costimulatory Signals

scholarly journals Mutation in Fas Ligand Impairs Maturation of Thymocytes Bearing Moderate Affinity T Cell Receptors

2003 ◽  
Vol 198 (2) ◽  
pp. 349-360 ◽  
Author(s):  
Tamar E. Boursalian ◽  
Pamela J. Fink
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Activation ◽  
T Cell Receptors ◽  
Cell Activation ◽  
Fas Ligand ◽  
Costimulatory Molecule ◽  
Thymocyte Development ◽  
Cell Receptors ◽  
Accessory Molecule

Fas ligand, best known as a death-inducer, is also a costimulatory molecule required for maximal proliferation of mature antigen-specific CD4+ and CD8+ T cells. We now extend the role of Fas ligand by showing that it can also influence thymocyte development. T cell maturation in some, but not all, strains of TCR transgenic mice is severely impaired in thymocytes expressing mutant Fas ligand incapable of interacting with Fas. Mutant Fas ligand inhibits neither negative selection nor death by neglect. Instead, it appears to modulate positive selection of thymocytes expressing both class I– and class II–restricted T cell receptors of moderate affinity for their positively selecting ligands. Fas ligand is therefore an inducer of death, a costimulator of peripheral T cell activation, and an accessory molecule in positive selection.

scholarly journals Association of CD28 IVS3 +17T/C Polymorphism with Soluble CD28 in Rheumatoid Arthritis

2011 ◽  
Vol 30 (1) ◽  
pp. 25-29 ◽  
Author(s):  
I. Y. Ledezma-Lozano ◽  
J. J. Padilla-Martínez ◽  
S. D. Leyva-Torres ◽  
I. Parra-Rojas ◽  
M. G. Ramírez-Dueñas ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Activation ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Serum Levels ◽  
Unknown Etiology ◽  
Clinical Activity ◽  
Western Mexico

Objective:Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity.Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.Results:RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p= 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p= 0.026). The RA patients showed higher sCD28 serum levels than HS (p= 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p= 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272;p= 0.016), was found.Conclusion:The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.

scholarly journals Both Maturation and Survival of Human Dendritic Cells are Impaired in the Presence of Anergic/Suppressor T Cells

2003 ◽  
Vol 10 (1) ◽  
pp. 61-65 ◽  
Author(s):  
L. Frasca ◽  
C. Scottà ◽  
G. Lombardi ◽  
E. Piccolella
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
T Cell Suppression ◽  
Cell Suppression ◽  
Anergic T Cells ◽  
Human Dendritic Cells

T cell suppression is a well established phenomenon, but the mechanisms involved are still a matter of debate. Mouse anergic T cells were shown to suppress responder T cell activation by inhibiting the antigen presenting function of DC. In the present work we studied the effects of co-culturing human anergic CD4+T cells with autologous dendritic cells (DC) at different stages of maturation. Either DC maturation or survival, depending on whether immature or mature DC where used as APC, was impaired in the presence of anergic cells. Indeed, MHC and costimulatory molecule up-regulation was inhibited in immature DC, whereas apoptotic phenomena were favored in mature DC and consequently in responder T cells. Defective ligation of CD40 by CD40L (CD154) was responsible for CD95-mediated and spontaneous apoptosis of DC as well as for a failure of their maturation process. These findings indicate that lack of activation of CD40 on DC by CD40L-defective anergic cells might be the primary event involved in T cell suppression and support the role of CD40 signaling in regulating both activation and survival of DC.

scholarly journals Release of serine/threonine-phosphorylated adaptors from signaling microclusters down-regulates T cell activation

2011 ◽  
Vol 195 (5) ◽  
pp. 839-853 ◽  
Author(s):  
Rémi Lasserre ◽  
Céline Cuche ◽  
Ronnie Blecher-Gonen ◽  
Evgeny Libman ◽  
Elise Biquand ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Cell Receptors ◽  
Cell Activation ◽  
Serine Phosphorylation ◽  
Cooperative Binding ◽  
Cell Responses ◽  
Immunological Synapses ◽  
Signaling Microclusters ◽  
The Stability

Antigen recognition within immunological synapses triggers and sustains T cell activation by nucleating protein microclusters that gather T cell receptors (TCRs), kinases, and adaptors. Dissipation of these microclusters results in signal termination, but how this process is regulated is unclear. In this paper, we reveal that release of the adaptors SLP76 and GADS from signaling microclusters is induced by the serine/threonine protein kinase HPK1 and that phosphorylation of GADS plays a major role in this process. We found that HPK1 was recruited into microclusters and triggered their dissipation by inducing the phosphorylation of a threonine-containing motif of GADS, together with the previously described serine phosphorylation of SLP76. These events induced the cooperative binding of 14-3-3 proteins to SLP76–GADS complexes, leading to their uncoupling from the transmembrane adaptor LAT and consequently reducing microcluster persistence and activation-induced gene transcription. These results demonstrate that serine/threonine phosphorylation of multiple TCR-proximal effectors controls the stability of signaling microclusters, thereby determining the intensity of T cell responses.

Enhanced B7-2 Gene Expression by Interferon-γ in Human Monocytic Cells Is Controlled Through Transcriptional and Posttranscriptional Mechanisms

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1782-1789 ◽  
Author(s):  
R.E. Curiel ◽  
C.S. Garcia ◽  
S. Rottschafer ◽  
M.C. Bosco ◽  
I. Espinoza-Delgado
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Costimulatory Molecule ◽  
Interferon Γ ◽  
Monocytic Cell ◽  
Monocytic Cells ◽  
Enhanced Expression ◽  
Ifn Γ

B7-2 is a costimulatory molecule expressed on professional antigen-presenting cells that provides T cells with a critical signal resulting in T-cell activation. Interferon-γ (IFN-γ) enhances B7-2 protein expression in monocytic cells. However, the molecular mechanisms controlling the enhanced expression of B7-2 are poorly understood. Northern blot and flow cytometry analysis revealed that human monocytes and the human monocytic cell line MonoMac6 (MM6) constitutively expressed B7-2 mRNA and protein and IFN-γ treatment further enhanced the expression of both molecules. The ability of IFN-γ to enhance B7-2 mRNA was evident at the dose of 31 U/mL and reached plateau levels at 500 U/mL. The effects of IFN-γ on B7-2 mRNA expression were time dependent and occurred within 3 hours of treatment and increased through 24 hours. In vitro transcription assays and mRNA stability experiments showed that IFN-γ increases both transcriptional activity and the stability of B7-2 mRNA. Treatment of MM6 cells with cycloheximide showed that de novo protein synthesis was not required for the IFN-γ–enhanced expression of B7-2 mRNA. Overall, these studies show for the first time that IFN-γ–enhanced expression of B7-2 protein in human monocytic cells is controlled at the gene level through a dual mechanism involving transcriptional and posttranscriptional mechanisms.

scholarly journals Spatiotemporal Basis of CTLA-4 Costimulatory Molecule-Mediated Negative Regulation of T Cell Activation

Immunity ◽  
2010 ◽  
Vol 33 (3) ◽  
pp. 326-339 ◽  
Author(s):  
Tadashi Yokosuka ◽  
Wakana Kobayashi ◽  
Masako Takamatsu ◽  
Kumiko Sakata-Sogawa ◽  
Hu Zeng ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Negative Regulation

scholarly journals Opposing Effects of Polyadenylation on the Stability of Edited and Unedited Mitochondrial RNAs in Trypanosoma brucei

2005 ◽  
Vol 25 (5) ◽  
pp. 1634-1644 ◽  
Author(s):  
Chia-Ying Kao ◽  
Laurie K. Read
Keyword(s):  
Trypanosoma Brucei ◽  
Rna Stability ◽  
Protein S ◽  
Rna Degradation ◽  
Nucleotide Composition ◽  
Rna Turnover ◽  
Degradation Reactions ◽  
The Stability ◽  
Opposing Effects

ABSTRACT Mitochondrial RNAs in Trypanosoma brucei undergo posttranscriptional RNA editing and polyadenylation. We previously showed that polyadenylation stimulates turnover of unedited RNAs. Here, we investigated the role of polyadenylation in decay of edited RPS12 RNA. In in vitro turnover assays, nonadenylated fully edited RNA degrades significantly faster than its unedited counterpart. Rapid turnover of nonadenylated RNA is facilitated by editing at just six editing sites. Surprisingly, in direct contrast to unedited RNA, turnover of fully edited RNA is dramatically slowed by addition of a poly(A)20 tail. The same minimal edited sequence that stimulates decay of nonadenylated RNA is sufficient to switch the poly(A) tail from a destabilizing to a stabilizing element. Both nucleotide composition and length of the 3′ extension are important for stabilization of edited RNA. Titration of poly(A) into RNA degradation reactions has no effect on turnover of polyadenylated edited RNA. These results suggest the presence of a protective protein(s) that simultaneously recognizes the poly(A) tail and small edited element and which blocks the action of a 3′-5′ exonuclease. This study provides the first evidence for opposing effects of polyadenylation on RNA stability within a single organelle and suggests a novel and unique regulation of RNA turnover in this system.

Sign in / Sign up

Export Citation Format

Share Document