A highly conserved sequence associated with the HIV gp41 loop region is an immunomodulator of antigen-specific T cells in mice

Blood ◽  
2013 ◽  
Vol 121 (12) ◽  
pp. 2244-2252 ◽  
Author(s):  
Avraham Ashkenazi ◽  
Omri Faingold ◽  
Nathali Kaushansky ◽  
Avraham Ben-Nun ◽  
Yechiel Shai
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Conserved Sequence ◽  
Loop Region ◽  
Key Points ◽  
Hiv Gp41

Key PointsA motif associated with the gp41 loop region of HIV interacts with the T-cell receptor complex and inactivates antigen-specific T cells.

scholarly journals Circulating CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Individuals Have Impaired Function and Downmodulate CD3ζ, the Signaling Chain of the T-Cell Receptor Complex

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 585-594 ◽  
Author(s):  
Linda A. Trimble ◽  
Judy Lieberman
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus ◽  
Specific Cytotoxicity

Although human immunodeficiency virus (HIV)-infected subjects without acquired immunodeficiency syndrome have a high frequency of HIV-specific CD8 T lymphocytes, freshly isolated lymphocytes frequently lack detectable HIV-specific cytotoxicity. However, this effector function becomes readily apparent after overnight culture. To investigate reasons for T-cell dysfunction, we analyzed T-cell expression of the cytolytic protease granzyme A and of CD3ζ, the signaling component of the T-cell receptor complex. An increased proportion of CD4 and CD8 T cells from HIV-infected donors contain granzyme A, consistent with the known increased frequency of activated T cells. In 28 HIV-infected donors with mild to advanced immunodeficiency, a substantial fraction of circulating T cells downmodulated CD3ζ (fraction of T cells expressing CD3ζ, 0.74 ± 0.16 v 1.01 ± 0.07 in healthy donors; P < .0000005). CD3ζ expression is downregulated more severely in CD8 than CD4 T cells, decreases early in infection, and correlates with declining CD4 counts and disease stage. CD3ζ expression increases over 6 to 16 hours of culture in an interleukin-2–dependent manner, coincident with restoration of viral-specific cytotoxicity. Impaired T-cell receptor signaling may help explain why HIV-specific cytotoxic T lymphocytes fail to control HIV replication.

scholarly journals Stimulation of T cells through the CD3/T-cell receptor complex: role of cytoplasmic calcium, protein kinase C translocation, and phosphorylation of pp60c-src in the activation pathway.

1987 ◽  
Vol 7 (2) ◽  
pp. 650-656 ◽  
Author(s):  
J A Ledbetter ◽  
L E Gentry ◽  
C H June ◽  
P S Rabinovitch ◽  
A F Purchio
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Solid Phase ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Receptor Complex ◽  
Kinase C ◽  
Stimulation Of

Stimulation of T cells or the Jurkat T-cell line with soluble antibodies to the CD3/T-cell receptor complex causes mobilization of cytoplasmic Ca2+, which is blocked by pertussis toxin but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and translocation of protein kinase C activity from the cytoplasm to the membrane. Such stimulation also causes phosphorylation of pp60c-src at an amino-terminal serine residue. These activities are consistent with induction of phosphatidylinositol metabolism after antibody binding. Anti-CD3 stimulation with antibody in solution, however, does not cause Jurkat cells to release interleukin 2 and blocks rather than induces proliferation of T cells. Induction of interleukin 2 production by Jurkat cells and proliferation by normal T cells requires anti-CD3 stimulation with antibody on a solid support, such as Sepharose beads or a plastic dish. Thus, we examined phosphorylation of pp60c-src after stimulation of Jurkat cells with anti-CD3 in solution or on solid phase. Both of these caused serine phosphorylation of pp60c-src that was indistinguishable even after 4 h of stimulation. These results indicate that the mode of anti-CD3 stimulation (in solution or on solid phase) controls a cellular function that modifies the consequences of signal transduction through phosphatidylinositol turnover.

Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures

Nature ◽  
1989 ◽  
Vol 337 (6203) ◽  
pp. 181-184 ◽  
Author(s):  
Christopher A. Smith ◽  
Gwyn T. Williams ◽  
Rosetta Kingston ◽  
Eric J. Jenkinson ◽  
John J. T. Owen
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex

scholarly journals Identification of a T3/T cell receptor complex in chickens.

1986 ◽  
Vol 164 (1) ◽  
pp. 375-380 ◽  
Author(s):  
C L Chen ◽  
L L Ager ◽  
G L Gartland ◽  
M D Cooper
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Membranes ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Hemopoietic Stem Cells ◽  
Large Numbers

A mouse mAb, CT-3, recognizes on chicken T cells a complex of three polypeptides, Mr 20,000, 19,000, and 17,000, two of which are N-glycosylated. The CT-3 antibody is mitogenic for chicken T cells, and it coprecipitates two additional polypeptides of Mr 49,000 and 38,000 in lysates of T cell membranes. Ontogeny studies revealed that 5-6 d after thymic influx of hemopoietic stem cells, their thymocyte progeny begin to express the T3/TCR complex. After hatching 1 wk later, the CT-3+ cells begin splenic migration in large numbers.

scholarly journals Ultrasmall silica nanoparticles directly ligate the T cell receptor complex

2019 ◽  
Vol 117 (1) ◽  
pp. 285-291 ◽  
Author(s):  
Bradley Vis ◽  
Rachel E. Hewitt ◽  
Tom P. Monie ◽  
Camilla Fairbairn ◽  
Suzanne D. Turner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Silica Nanoparticles ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Orthosilicic Acid ◽  
Receptor Complex ◽  
The Impact

The impact of ultrasmall nanoparticles (<10-nm diameter) on the immune system is poorly understood. Recently, ultrasmall silica nanoparticles (USSN), which have gained increasing attention for therapeutic applications, were shown to stimulate T lymphocytes directly and at relatively low-exposure doses. Delineating underlying mechanisms and associated cell signaling will hasten therapeutic translation and is reported herein. Using competitive binding assays and molecular modeling, we established that the T cell receptor (TCR):CD3 complex is required for USSN-induced T cell activation, and that direct receptor complex–particle interactions are permitted both sterically and electrostatically. Activation is not limited to αβ TCR-bearing T cells since those with γδ TCR showed similar responses, implying that USSN mediate their effect by binding to extracellular domains of the flanking CD3 regions of the TCR complex. We confirmed that USSN initiated the signaling pathway immediately downstream of the TCR with rapid phosphorylation of both ζ-chain–associated protein 70 and linker for activation of T cells protein. However, T cell proliferation or IL-2 secretion were only triggered by USSN when costimulatory anti-CD28 or phorbate esters were present, demonstrating that the specific impact of USSN is in initiation of the primary, nuclear factor of activated T cells-pathway signaling from the TCR complex. Hence, we have established that USSN are partial agonists for the TCR complex because of induction of the primary T cell activation signal. Their ability to bind the TCR complex rapidly, and then to dissolve into benign orthosilicic acid, makes them an appealing option for therapies targeted at transient TCR:CD3 receptor binding.

scholarly journals TCF1 expression marks self-renewing human CD8+ T cells

2018 ◽  
Vol 2 (14) ◽  
pp. 1685-1690 ◽  
Author(s):  
Radomir Kratchmarov ◽  
Arthur M. Magun ◽  
Steven L. Reiner
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Human Blood ◽  
Cell Receptor ◽  
Receptor Stimulation ◽  
Key Points

Key Points Human blood CD8+ T cells express distinct levels of TCF1, defining quiescent vs effector populations. TCF1-hi cells proliferate and uniquely self-renew following T-cell receptor stimulation to produce both TCF1-hi and TCF1-low cells.

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