scholarly journals Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation

1982 ◽  
Vol 155 (4) ◽  
pp. 1086-1099 ◽  
Author(s):  
E Heber-Katz ◽  
RH Schwartz ◽  
LA Matis ◽  
C Hannum ◽  
T Fairwell ◽  
...  
Keyword(s):  
T Cell ◽  
Cytochrome C ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Clone ◽  
Cross Reactivity ◽  
Histocompatibility Complex ◽  
Cell Clones ◽  
T Cell Clone ◽  
Antigen Presenting

Previous studies from our laboratory showed that B 10.A mice are high responders to pigeon cytochrome c fragment 81-104, whereas B 10.A(5R) mice are low responders. In the present studies, the C-terminal cyanogen bromide cleavage fragment and homologous synthetic peptides of tobacco horn worm moth cytochrome c were shown to be immunogenic in both B10.A and B10.A(5R) mice. These strains, however, showed different patterns of cross-reactivity when immune lymph node T cells were stimulated with cytochrome c fragments from other species. To examine the two patterns of responsiveness at a clonal level, cytochrome c fragment-specific T cell hybridomas were made and found to secrete interleukin 2 in response to antigen. The patterns of cross- reactivity of these B 10.A and B 10.A(5R) clones were similar to that seen in the whole lymph node population. Surprisingly, when these clones were tested for major histocompatibility complex (MHC)-restricted antigen recognition, they were all found to respond to antigen with both B10.A and B10.A(5R) antigen-presenting cells (APC). Furthermore, the cross-reactivity pattern appeared to be largely determined by the genotype of the APC, not the genotype of the T cell clone. That is, a given T cell clone displayed a different fine specificity when assayed with B10.A or B10.A(5R) APC. This observation indicates that the APC MHC gene product and antigen interact during the stimulation of the T cell response and that as a consequence the specificity of antigen-induced T cell activation is influenced by these MHC gene products. (During the preparation of this manuscript it has come to our attention that results similar to our own, concerning the fine specificity of cytotoxic T cell clones, have been obtained by Dr. T. R. Hunig and Dr. M. J. Bevan, Massachusetts Institute of Technology, Boston, MA. T. R. Hunig and M. J. Bevan. 1981. Specificity of T-cell clones illustrates altered self hypothesis. Nature. 294:460.)

scholarly journals Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes.

1996 ◽  
Vol 184 (3) ◽  
pp. 811-819 ◽  
Author(s):  
L Biancone ◽  
M A Bowen ◽  
A Lim ◽  
A Aruffo ◽  
G Andres ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Divalent Cations ◽  
Membranous Glomerulonephritis ◽  
Murine Splenocytes ◽  
Cell Clones ◽  
Physiologic Function ◽  
Antigen Presenting

CD5 is a 67-kD glycoprotein that is expressed on most T lymphocytes and on a subset of mature B cells. Although its physiologic function is unknown, several lines of evidence suggest that CD5 may play a role in the regulation of T cell activation and in T cell-antigen presenting cell interactions. Using a CD5-immunoglobulin fusion protein (CD5Rg, for receptorglobulin) we have uncovered a new CD5 ligand (CD5L) expressed on the surface of activated splenocytes. Stimulation of murine splenocytes with anti-CD3 and anti-CD28 antibodies induce transient expression of CD5L on B lymphocytes that lasts for approximately 72 h. Binding of CD5Rg to activated splenocytes is trypsin resistant and independent of divalent cations. However, it is pronase sensitive and dependent on N-linked glycosylation of CD5, since treatment of CD5Rg with PNGaseF on N-glycanase completely abrogates its ability to bind activated splenocytes. It addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CD5L is distinct from CD72, which has been proposed to be a CD5 ligand. To determine whether CD5-CD5L interaction might play a role in vivo, we tested the effect of CD5Rg in a murine model of antibody-mediated membranous glomerulonephritis. Injection of CD5Rg was found to abrogate development of the disease. Taken together, our results help identify a novel ligand of CD5 and propose a role for CD5 in the regulation of immune responses.

scholarly journals IL4I1 Accelerates the Expansion of Effector CD8+ T Cells at the Expense of Memory Precursors by Increasing the Threshold of T-Cell Activation

2020 ◽  
Vol 11 ◽  
Author(s):  
Marie-Line Puiffe ◽  
Aurélie Dupont ◽  
Nouhoum Sako ◽  
Jérôme Gatineau ◽  
José L. Cohen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Clone

IL4I1 is an immunoregulatory enzyme that inhibits CD8 T-cell proliferation in vitro and in the tumoral context. Here, we dissected the effect of IL4I1 on CD8 T-cell priming by studying the differentiation of a transgenic CD8 T-cell clone and the endogenous repertoire in a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection. Unexpectedly, we show that IL4I1 accelerates the expansion of functional effector CD8 T cells during the first several days after infection and increases the average affinity of the elicited repertoire, supporting more efficient LCMV clearance in WT mice than IL4I1-deficient mice. Conversely, IL4I1 restrains the differentiation of CD8 T-cells into long-lived memory precursors and favors the memory response to the most immunodominant peptides. IL4I1 expression does not affect the phenotype or antigen-presenting functions of dendritic cells (DCs), but directly reduces the stability of T-DC immune synapses in vitro, thus dampening T-cell activation. Overall, our results support a model in which IL4I1 increases the threshold of T-cell activation, indirectly promoting the priming of high-affinity clones while limiting memory T-cell differentiation.

scholarly journals Requirements for Peptide-induced T Cell Receptor Downregulation on Naive CD8+ T Cells

1997 ◽  
Vol 185 (4) ◽  
pp. 641-652 ◽  
Author(s):  
Zeling Cai ◽  
Hidehiro Kishimoto ◽  
Anders Brunmark ◽  
Michael R. Jackson ◽  
Per A. Peterson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Biological Significance ◽  
Cell Receptor ◽  
Metabolic Inhibitors ◽  
Histocompatibility Complex ◽  
Antigen Presenting

The requirements for inducing downregulation of α/β T cell receptor (TCR) molecules on naive major histocompatibility complex class I–restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling.

scholarly journals Immunologically relevant peptide antigen exists on the presenting cell in a manner accessible to macromolecules in solution.

1986 ◽  
Vol 164 (5) ◽  
pp. 1440-1454 ◽  
Author(s):  
K B Cease ◽  
G Buckenmeyer ◽  
I Berkower ◽  
J York-Jolley ◽  
J A Berzofsky
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Antigen Processing ◽  
Cell Activation ◽  
Cell Clone ◽  
Sperm Whale ◽  
Amino Terminal ◽  
T Cell Clone

Although studies of the association of antigen with APC have been complicated by antigen-processing requirements, recent studies have suggested that immunologically relevant antigen should be present on the APC surface. Nevertheless, blocking of antigen presentation with antibody to the antigen has not been demonstrable in most systems. To study this problem we developed a system using avidin to block presentation of amino-terminal biotinylated synthetic peptide 132-146 of sperm whale myoglobin (B132) to a murine T cell clone specific for this site in association with I-Ed. greater than 95% specific inhibition was observed with doses of B132 equipotent to unmodified peptide. Specific blocking could be observed: (a) after pulsing APC with antigen, washing, and incubating for a chase period of 8-16 h before addition of avidin and T cells to assure adequate time for intracellular trafficking and maximal display of antigen on the cell surface, or (b) when monensin is present during the antigen pulse to inhibit such traffic. Therefore, the inhibition appeared to be occurring at the cell surface unless dissociation and reassociation were constantly occurring. To distinguish these, B10.GD APC (I-Ed-negative) were pulsed with antigen and cocultured with B10.D2 APC (I-Ed-positive). No detectable antigen presentation resulted. Thus, minimal dissociation and reassociation between antigen and APC occurs and, consequently, blocking by extracellular solution-phase binding of avidin to antigen is unlikely. Taken together, these data suggest that the blocking is occurring at the cell surface. Thus, under physiologic conditions, immunologically relevant antigen necessary for T cell activation appears to be present on the APC surface and is freely accessible to macromolecules the size of avidin. These findings hold specific implications for models of antigen presentation for T cell recognition.

scholarly journals The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-Ia.

1984 ◽  
Vol 159 (5) ◽  
pp. 1397-1412 ◽  
Author(s):  
J Kaye ◽  
C A Janeway
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
T Cell Activation ◽  
Single Molecule ◽  
Cell Activation ◽  
Cell Clone ◽  
Antigen Receptors ◽  
Helper T Cell ◽  
Fab Fragment ◽  
T Cell Clone

We characterize a monoclonal antibody directed against the antigen/Ia receptor of a cloned helper T cell line that induced T cell clone proliferation and T cell clone-dependent B cell proliferation at antibody concentrations as low as 10(-11) M. A Fab fragment of this antibody was not stimulatory, implicating cross-linking of antigen receptors as the primary signal for T cell activation. The Fab fragment inhibited activation of this clone by both allogeneic Ia and antigen plus self-Ia, but not by the nonspecific stimulators concanavalin A and rabbit anti-mouse brain serum. This strongly supports the hypothesis that a single molecule mediates both self-Ia plus antigen and non-self-Ia recognition. This molecule is presumably the disulfide-linked heterodimer comprised of 42,000 mol wt acidic and basic subunits precipitated by this monoclonal antibody. The cell surface and internal precursor forms of this protein are also identified. In addition, the response to allogeneic Ia stimulation was more readily inhibited by the Fab fragment than was the response to antigen plus self-Ia, suggesting that alloreactivity reflects a low affinity interaction with a ligand represented at high frequency on the stimulatory cell.

scholarly journals Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling

1998 ◽  
Vol 188 (9) ◽  
pp. 1575-1586 ◽  
Author(s):  
Loralee Haughn ◽  
Bernadine Leung ◽  
Lawrence Boise ◽  
André Veillette ◽  
Craig Thompson ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Membrane ◽  
T Cell ◽  
T Cell Activation ◽  
Protein Tyrosine Kinase ◽  
Cell Activation ◽  
Cell Clone ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
T Cell Clone

T cell activation and clonal expansion is the result of the coordinated functions of the receptors for antigen and interleukin (IL)-2. The protein tyrosine kinase p56lck is critical for the generation of signals emanating from the T cell antigen receptor (TCR) and has also been demonstrated to play a role in IL-2 receptor signaling. We demonstrate that an IL-2–dependent, antigen-specific CD4+ T cell clone is not responsive to anti-TCR induced growth when propagated in IL-2, but remains responsive to both antigen and CD3ε-specific monoclonal antibody. Survival of this IL-2–dependent clone in the absence of IL-2 was supported by overexpression of exogenous Bcl-xL. Culture of this clonal variant in the absence of IL-2 rendered it susceptible to anti-TCR–induced signaling, and correlated with the presence of kinase-active Lck associated with the plasma membrane. The same phenotype is observed in primary, resting CD4+ T cells. Furthermore, the presence of kinase active Lck associated with the plasma membrane correlates with the presence of ZAP 70–pp21ζ complexes in both primary T cells and T cell clones in circumstances of responsive anti-TCR signaling. The results presented demonstrate that IL-2 signal transduction results in the functional uncoupling of the TCR complex through altering the subcellular distribution of kinase-active Lck.

scholarly journals The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.

1984 ◽  
Vol 159 (1) ◽  
pp. 318-323 ◽  
Author(s):  
D Ramarli ◽  
B Parodi ◽  
M Fabbi ◽  
G Corte ◽  
A Lanzavecchia
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Activation ◽  
Cell Clone ◽  
B Cell Activation ◽  
Stimulator Cell ◽  
Cytotoxic Response ◽  
Cell Clones ◽  
T Cell Clone ◽  
Alloreactive T Cell

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.

scholarly journals Human T cells cannot act as autonomous antigen-presenting cells, but induce tolerance in antigen-specific and alloreactive responder cells.

1992 ◽  
Vol 176 (3) ◽  
pp. 875-880 ◽  
Author(s):  
S Sidhu ◽  
S Deacock ◽  
V Bal ◽  
J R Batchelor ◽  
G Lombardi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Antigen Presenting Cells ◽  
Accessory Cell ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones ◽  
T Cell Clone ◽  
Antigen Presenting

The ability of two HLA-DR-expressing human T cell clones to function as antigen-presenting cells (APC) was investigated using highly purified T cells. The results demonstrated that these T cell clones are unable to act as autonomous APC, and that recognition of nominal or alloantigens on the surface of T cells leads to a state of nonresponsiveness. The first observation was that a T cell clone with specificity for the 306-324 peptide of influenza hemagglutinin (HA), and raised from a DR1 responder, exhibited apparent degeneracy of major histocompatibility complex restriction when cultured with peptide in the presence of peripheral blood mononuclear cells (PBMC) expressing a wide variety of structurally unrelated DR types. However, when the PBMC were pulsed with peptide and washed before coculture with the clone, peptide was exclusively recognized with DR1Dw1. This implied that in the presence of soluble peptide the T cells were displaying ligand to each other, and that the third-party APC were providing costimulatory signals. To test the ability of T cells to act as autonomous APC, accessory cell-free preparations of two DR1-restricted clones were cultured with peptide in the presence or the absence of added B cell APC. T cell purity was established by the absence of proliferation in response to the mitogen phytohemagglutinin (PHA). PHA-nonresponsive T cells were completely unable to proliferate in response to peptide alone; furthermore, preculture of the HA-specific clone, in the complete absence of accessory cells, with the same concentration of peptide (1 microgram/ml) that induced optimal proliferation when presented by conventional APC, led to profound nonresponsiveness. The same phenomenon was also observed when two of three anti-DR1 alloreactive T cell clones were precultured with a DR1-expressing T cell clone. The ability of the DR1-expressing clone to induce nonresponsiveness in anti-DR1 clones correlated with recognition of the DR1 alloantigen on the DR1-expressing clone.

scholarly journals Inhibition of Ly-6A antigen expression prevents T cell activation.

1990 ◽  
Vol 172 (1) ◽  
pp. 115-120 ◽  
Author(s):  
P M Flood ◽  
J P Dougherty ◽  
Y Ron
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Antisense Oligonucleotides ◽  
Cell Activation ◽  
Cell Clone ◽  
Spleen Cells ◽  
Con A ◽  
Normal Spleen ◽  
T Cell Clone ◽  
Stimulation Of

Antisense oligonucleotides complementary to the 5' end of the mRNA encoding the Ly-6A protein were used to block the expression of that protein. Using this approach we could inhibit the expression of Ly-6A by 60-80% in antigen-primed lymph node (LN) T cells as well as in the D10 T cell clone. Inhibition of Ly-6 expression resulted in the inability to restimulate in vitro, antigen-primed T cells. It also blocked the activation of normal spleen cells by Con A, monoclonal antibody (mAb) to CD3, and mAb to Ly-6. In contrast, stimulation of normal spleen cells with the pharmacological agents PMA + ionomycin were unaffected by the inhibition of Ly-6 expression. Similar results were obtained with the D10 T cell clone; stimulation with Con A + interleukin 1 (IL-1), antigen-presenting cells (APC), or the clonotypic antibody + IL-1 was greatly reduced in the presence of antisense oligonucleotides to Ly-6. Stimulation with PMA + ionomycin was again unaffected. We also studied the effect of antisense oligonucleotides on stimulation of preactivated D10 cells. Preactivation of D10 cells with Con A + IL-1 renders them receptive to secondary stimulation by other lymphokines. In this case, antisense oligonucleotides to Ly-6 had no effect on secondary activation with IL-2, IL-4 + IL-1, or PMA + ionomycin. We conclude from these studies that Ly-6 expression is required for T cell receptor (TCR)-mediated T cell activation.

Visualizing Quantum Dot Labeled ORAI1 Proteins in Intact Cells Via Correlative Light and Electron Microscopy

2016 ◽  
Vol 22 (4) ◽  
pp. 902-912 ◽  
Author(s):  
Diana B. Peckys ◽  
Dalia Alansary ◽  
Barbara A. Niemeyer ◽  
Niels de Jonge
Keyword(s):  
Electron Microscopy ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Calcium Release ◽  
Cell Clone ◽  
Pair Correlation ◽  
Light And Electron Microscopy ◽  
Intact Cells ◽  
T Cell Clone

AbstractORAI1 proteins are ion channel subunits and the essential pore-forming units of the calcium release-activated calcium channel complex essential for T-cell activation and many other cellular processes. In this study, we used environmental scanning electron microscopy (ESEM) with scanning transmission electron microscopy (STEM) detection to image plasma membrane expressed ORAI1 proteins in whole Jurkat T cells in the liquid state. Utilizing a stably transfected Jurkat T cell clone expressing human ORAI1 with an extracellular human influenza hemagglutinin (HA) tag we investigated if liquid-phase STEM can be applied to detect recombinant surface expressed protein. Streptavidin coated quantum dots were coupled in a one-to-one stoichiometry to ORAI1 proteins detected by biotinylated anti-HA fragmented antibody fragments. High-resolution electron microscopic images revealed the individual label locations from which protein pair distances were determined. These data were analyzed using the pair correlation function and, in addition, an analysis of cluster size and frequency was performed. ORAI1 was found to be present in hexamers in a small fraction only, and ORAI1 resided mostly in monomers and dimers.

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