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 Superresolution imaging reveals nanometer- and micrometer-scale spatial distributions of T-cell receptors in lymph nodes

2016 ◽  
Vol 113 (26) ◽  
pp. 7201-7206 ◽  
Author(s):  
Ying S. Hu ◽  
Hu Cang ◽  
Björn F. Lillemeier
Keyword(s):  
T Cells ◽  
Plasma Membrane ◽  
T Cell ◽  
Lymph Nodes ◽  
T Cell Activation ◽  
T Cell Receptors ◽  
Cell Activation ◽  
Cell Receptors ◽  
Micrometer Scale

T cells become activated when T-cell receptors (TCRs) recognize agonist peptides bound to major histocompatibility complex molecules on antigen-presenting cells. T-cell activation critically relies on the spatiotemporal arrangements of TCRs on the plasma membrane. However, the molecular organizations of TCRs on lymph node-resident T cells have not yet been determined, owing to the diffraction limit of light. Here we visualized nanometer- and micrometer-scale TCR distributions in lymph nodes by light sheet direct stochastic optical reconstruction microscopy (dSTORM) and structured illumination microscopy (SIM). This dSTORM and SIM approach provides the first evidence, to our knowledge, of multiscale reorganization of TCRs during in vivo immune responses. We observed nanometer-scale plasma membrane domains, known as protein islands, on naïve T cells. These protein islands were enriched within micrometer-sized surface areas that we call territories. In vivo T-cell activation caused the TCR territories to contract, leading to the coalescence of protein islands and formation of stable TCR microclusters.

scholarly journals Correlation Between the Number of T Cell Receptors Required for T Cell Activation and TCR–Ligand Affinity

Immunity ◽  
1996 ◽  
Vol 5 (2) ◽  
pp. 137-146 ◽  
Author(s):  
Beth A. Schodin ◽  
Theodore J. Tsomides ◽  
David M. Kranz
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Cell Receptors ◽  
Cell Activation ◽  
Cell Receptors ◽  
Ligand Affinity

scholarly journals T-Cell Receptor Clustering Methods Used for Single Cell Analysis: Potential Application in Oncology

2021 ◽  
pp. 1-5
Author(s):  
Jason Paul Buttigieg ◽  
Jason Paul Buttigieg ◽  
Kristian Helmerson ◽  
Brendon Coventry
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Immune Activation ◽  
T Cell Receptors ◽  
Cell Activation ◽  
Cell Types ◽  
Current Evidence ◽  
Receptor Clustering ◽  
Cell Receptors

We know that T-cell activation and effector function is integral for cancer cell destruction in immunotherapeutic treatment in oncology. The fundamental behaviour of T-cells at the time of activation is poorly understood but is likely to be central to this action. Cellular clustering occurs on at least two levels: gathering of multiple mobile cells of similar type, and aggregation between different cell types. Receptors are implicated in both of these processes. Analysis of receptor clustering is a different process whereby receptors form clusters on the cell membrane surface and can be studied to determine their relationship to immune activation. Receptor clustering has been shown to occur in some (perhaps all) cell types, but little is known about this phenomenon, particularly in T-lymphocytes. T-Cell Receptors (TCRs) which are important for the activation of T-lymphocytes. T-cell receptors, also known as cluster of differentiation 3 (CD3) molecules, bind specific antigen to create intracellular signaling in the process of T-cell activation as part of the immune response. The detail of how TCRs physically behave on the T-lymphocyte surface and specifically how they cluster remains unclear, including during the early phases of initiation of immune activation in the T-cell response. The aim of this review is to investigate how receptor clustering that has been studied, can be more effectively studied in the future and what the current evidence suggests about TCR clustering/T-cell activity relationships.

scholarly journals Itm2a Is Induced during Thymocyte Selection and T Cell Activation and Causes Downregulation of Cd8 When Overexpressed in Cd4+Cd8+ Double Positive Thymocytes

1999 ◽  
Vol 190 (2) ◽  
pp. 217-228 ◽  
Author(s):  
Jacqueline Kirchner ◽  
Michael J. Bevan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Activation ◽  
Antigen Processing ◽  
Cell Activation ◽  
Proximal Promoter ◽  
Cell Surface Expression ◽  
Thymocyte Development ◽  
Double Positive

To identify novel genes that are involved in positive selection of thymocytes, we performed polymerase chain reaction (PCR)-based subtractive hybridization between selecting and nonselecting thymi. OT-1 T cell receptor (TCR) transgenic thymocytes on a recombination activating gene (RAG) null background are efficiently selected into the CD8 lineage in H-2b mice (RAG-2−/−OT-1, selecting thymi), but are not selected on a transporter associated with antigen processing (TAP) null background (RAG-2−/−TAP-1−/−OT-1, nonselecting thymi). We report here our studies of one gene, ITM2A, whose expression is dramatically higher in T cells in the selecting thymus. The expression pattern of ITM2A in thymocyte subsets correlates with upregulation during positive selection. In addition, ITM2A expression is higher in the thymus than in either the spleen or lymph nodes, but can be upregulated in peripheral T cells upon activation. ITM2A expression was also induced in RAG-2−/− thymocytes in vivo upon CD3 cross-linking. We demonstrate that ITM2A is a type II membrane glycoprotein that exists as two species with apparent Mr of 45 and 43 kD and appears to localize primarily to large cytoplasmic vesicles and the Golgi apparatus, but is also expressed on the cell surface. Expression on the surface of EL4 cells increases with activation by phorbol myristate acetate (PMA) and ionomycin. Finally, overexpression of ITM2A under control of the lck proximal promoter in mice results in partial downregulation of CD8 in CD4+CD8+ double positive (DP) thymocytes, and a corresponding increase in the number of CD4+CD8lo thymocytes. Possible roles for this novel activation marker in thymocyte development are discussed.

High affinity T cell receptors from yeast display libraries block T cell activation by superantigens11Edited by I. A. Wilson

2001 ◽  
Vol 307 (5) ◽  
pp. 1305-1315 ◽  
Author(s):  
Michele C Kieke ◽  
Eric Sundberg ◽  
Eric V Shusta ◽  
Roy A Mariuzza ◽  
K.Dane Wittrup ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Cell Receptors ◽  
Cell Activation ◽  
Yeast Display ◽  
Cell Receptors ◽  
High Affinity

scholarly journals Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers

Nature ◽  
2021 ◽  
Author(s):  
Justina X. Caushi ◽  
Jiajia Zhang ◽  
Zhicheng Ji ◽  
Ajay Vaghasia ◽  
Boyang Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
T Cell Receptors ◽  
Tumour Microenvironment ◽  
Lung Cancers ◽  
Cell Receptors ◽  
Interleukin 7

AbstractPD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3 in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a ‘barcode’ to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein–Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThigh TRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.

scholarly journals The mouse vitronectin receptor is a T cell activation antigen.

1991 ◽  
Vol 173 (2) ◽  
pp. 343-347 ◽  
Author(s):  
K Moulder ◽  
K Roberts ◽  
E M Shevach ◽  
J E Coligan
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphoid Cells ◽  
Vitronectin Receptor ◽  
Cell Functions ◽  
Murine Homologue ◽  
Accessory Molecule ◽  
T Cell Lines ◽  
Activation Antigen

In this report, we demonstrate that the T cell activation antigen, recognized by monoclonal antibody H9.2B8, is the murine homologue of the vitronectin receptor (VNR) and, thereby, we provide initial evidence that VNR is expressed on lymphoid cells. VNR is expressed on a variety of T cell lines, tumors, and Con A-activated splenocytes, but not resting T cells, and is capable of binding to the extracellular matrix proteins fibronectin, fibrinogen, and vitronectin, via the tripeptide sequence RGD. There was no evidence of novel beta chains pairing with the VNR alpha chain, as has been demonstrated in some human cells. In view of recent studies demonstrating that this molecule functions as an accessory molecule in T cell activation, the VNR may play an important role in mouse T cell functions.

scholarly journals A Role for the Tec Family Tyrosine Kinase Txk in T Cell Activation and Thymocyte Selection

1999 ◽  
Vol 190 (10) ◽  
pp. 1427-1438 ◽  
Author(s):  
Connie L. Sommers ◽  
Ronald L. Rabin ◽  
Alexander Grinberg ◽  
Henry C. Tsay ◽  
Joshua Farber ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Positive Selection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Receptor ◽  
Calcium Signal ◽  
Protein Tyrosine

Summary Recent data indicate that several members of the Tec family of protein tyrosine kinases function in antigen receptor signal transduction. Txk, a Tec family protein tyrosine kinase, is expressed in both immature and mature T cells and in mast cells. By overexpressing Txk in T cells throughout development, we found that Txk specifically augments the phospholipase C (PLC)-γ1–mediated calcium signal transduction pathway upon T cell antigen receptor (TCR) engagement. Although Txk is structurally different from inducible T cell kinase (Itk), another Tec family member expressed in T cells, expression of the Txk transgene could partially rescue defects in positive selection and signaling in itk−/− mice. Conversely, in the itk+/+ (wild-type) background, overexpression of Txk inhibited positive selection of TCR transgenic thymocytes, presumably due to induction of cell death. These results identify a role for Txk in TCR signal transduction, T cell development, and selection and suggest that the Tec family kinases Itk and Txk perform analogous functions.

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