scholarly journals Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of CTL-target cell binding.

1984 ◽  
Vol 159 (3) ◽  
pp. 783-797 ◽  
Author(s):  
W E Biddison ◽  
P E Rao ◽  
M A Talle ◽  
G Goldstein ◽  
S Shaw
Keyword(s):  
Target Cell ◽  
Potential Role ◽  
Cytotoxic T Lymphocyte ◽  
Hla Antigens ◽  
Class Ii ◽  
Target Cells ◽  
Cell Recognition ◽  
Cell Binding ◽  
T Cell Recognition

The present study examines the potential role of the T4 molecule in functional cell-cell interactions between target cells and human cytotoxic T lymphocyte (CTL) clones that are specific for HLA class II alloantigens encoded by the SB locus. There were marked differences (greater than 30-fold) between the seven SB-specific clones studied with respect to their susceptibility to inhibition by anti-T4 as well as anti-T3 antibodies. We wished to test the hypothesis that such variation among the clones would be due to differences in clonal "affinity" for antigen. To quantitate differences among the CTL clones in the tightness with which they bind target cells, the clones were analyzed using a previously published assay of susceptibility of CTL-target cell conjugates to dissociation in the presence of unlabeled targets. The results revealed that the clones that were most susceptible to inhibition by anti-T4 and anti-T3 were the weakest target cell binders, and vice versa. Anti-T4 antibody could partially induce dissociation of functional CTL-target cell conjugates in the absence of any added cold targets. For the "highest affinity" clone such anti-T4 antibody-induced dissociation could be observed at 4 degrees C but not 23 degrees C. These results indicate that the T4 molecule is functionally involved in target cell binding by CTL, and raise the possibility that although it is easiest to demonstrate the function of the T4 molecule in "low affinity" clones, that function may also be operative in the "high affinity" clones.

T-cell recognition of a chimaeric class II/class I MHC molecule and the role of L3T4

Nature ◽  
1985 ◽  
Vol 317 (6036) ◽  
pp. 425-427 ◽  
Author(s):  
Hana Golding ◽  
James McCluskey ◽  
Terry I. Munitz ◽  
Ronald N. Germain ◽  
David H. Margulies ◽  
...  
Keyword(s):  
T Cell ◽  
Class Ii ◽  
Class I ◽  
Cell Recognition ◽  
Class I Mhc ◽  
T Cell Recognition

scholarly journals Role of self and foreign antigenic determinants in allogeneic and self-restricted cytotoxic T cell recognition.

1980 ◽  
Vol 152 (2) ◽  
pp. 405-418 ◽  
Author(s):  
R B Levy ◽  
P E Gilheany ◽  
G M Shearer
Keyword(s):  
Fluorescein Isothiocyanate ◽  
Cytotoxic T Cell ◽  
Antigenic Determinants ◽  
Target Cells ◽  
Cell Recognition ◽  
Spleen Cells ◽  
T Cell Recognition ◽  
Murine Spleen

Murine spleen cells were sensitized in vitro to H-2 disparate allogeneic spleen cells and assayed on syngeneic target cells conjugated with the trinitrophenyl (TNP)-self or the fluorescein isothiocyanate (FITC)-self haptens, or on syngeneic target cells expressing the male H-Y antigen (H-Y self). The results indicated that allo-induced cytotoxic T lymphocytes (CTL) contained effectors that lysed both hapten-self but not H-Y self targets. Furthermore, it was demonstrated that separate populations of those allogeneic CTL were responsible for the lysis of TNP-self and FITC-self targets. This study also showed that cytotoxic effectors generated against the H-Y antigen with lytic activity equal to or greater than that of an allogeneically induced CTL response were unable to lyse hapten-self targets. These findings provide the first evidence that H-2 alloantigens may be unique in their ability to induce effectors that lyse hapten-conjugated autologous targets. These observations are discussed with respect to the self and foreign antigenic determinants involved in allogeneic and self-restricted CTL models.

scholarly journals The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II

2015 ◽  
Vol 90 (1) ◽  
pp. 356-367 ◽  
Author(s):  
Laura L. Quinn ◽  
Luke R. Williams ◽  
Claire White ◽  
Calum Forrest ◽  
Jianmin Zuo ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Immune Evasion ◽  
Class Ii ◽  
Lytic Cycle ◽  
Class I ◽  
Target Cells ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Mhc Molecules

ABSTRACTThe ability of Epstein-Barr virus (EBV) to spread and persist in human populations relies on a balance between host immune responses and EBV immune evasion. CD8+cells specific for EBV late lytic cycle antigens show poor recognition of target cells compared to immediate early and early antigen-specific CD8+cells. This phenomenon is due in part to the early EBV protein BILF1, whose immunosuppressive activity increases with lytic cycle progression. However, published data suggest the existence of a hitherto unidentified immune evasion protein further enhancing protection against late EBV antigen-specific CD8+cells. We have now identified the late lytic BDLF3 gene as the missing link accounting for efficient evasion during the late lytic cycle. Interestingly, BDLF3 also contributes to evasion of CD4+cell responses to EBV. We report that BDLF3 downregulates expression of surface major histocompatibility complex (MHC) class I and class II molecules in the absence of any effect upon other surface molecules screened, including CD54 (ICAM-1) and CD71 (transferrin receptor). BDLF3 both enhanced internalization of surface MHC molecules and reduced the rate of their appearance at the cell surface. The reduced expression of surface MHC molecules correlated with functional protection against CD8+and CD4+T cell recognition. The molecular mechanism was identified as BDLF3-induced ubiquitination of MHC molecules and their subsequent downregulation in a proteasome-dependent manner.IMPORTANCEImmune evasion is a necessary feature of viruses that establish lifelong persistent infections in the face of strong immune responses. EBV is an important human pathogen whose immune evasion mechanisms are only partly understood. Of the EBV immune evasion mechanisms identified to date, none could explain why CD8+T cell responses to late lytic cycle genes are so infrequent and, when present, recognize lytically infected target cells so poorly relative to CD8+T cells specific for early lytic cycle antigens. The present work identifies an additional immune evasion protein, BDLF3, that is expressed late in the lytic cycle and impairs CD8+T cell recognition by targeting cell surface MHC class I molecules for ubiquitination and proteasome-dependent downregulation. Interestingly, BDLF3 also targets MHC class II molecules to impair CD4+T cell recognition. BDLF3 is therefore a rare example of a viral protein that impairs both the MHC class I and class II antigen-presenting pathways.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

scholarly journals Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL.

1996 ◽  
Vol 184 (2) ◽  
pp. 485-492 ◽  
Author(s):  
M A Alexander-Miller ◽  
G R Leggatt ◽  
A Sarin ◽  
J A Berzofsky
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocyte ◽  
Target Cells ◽  
High Dose ◽  
High Avidity ◽  
Apoptotic Pathway ◽  
Peptide Antigen ◽  
Kinetics Of ◽  
Selection Of

Experimental data suggest that negative selection of thymocytes can occur as a result of supraoptimal antigenic stimulation. It is unknown, however, whether such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show that CD8+ effector cytotoxic T lymphocytes (CTL) are susceptible to proliferative inhibition by high dose peptide antigen, leading to apoptotic death mediated by TNF-alpha release. Such inhibition is not reflected in the cytolytic potential of the CTL, since concentrations of antigen that are inhibitory for proliferation promote efficient lysis of target cells. Thus, although CTL have committed to the apoptotic pathway, the kinetics of this process are such that CTL function can occur before death of the CTL. The concentration of antigen required for inhibition is a function of the CTL avidity, in that concentrations of antigen capable of completely inhibiting high avidity CTL maximally stimulate low avidity CTL. Importantly, the inhibition can be detected in both activated and resting CTL. Blocking studies demonstrate that the CD8 molecule contributes significantly to the inhibitory signal as the addition of anti-CD8 antibody restores the proliferative response. Thus, our data support the model that mature CD8+ CTL can accommodate an activation signal of restricted intensity, which, if surpassed, results in deletion of that cell.

scholarly journals Cell-mediated lympholysis to H-2-matched target cells modified with a series of nitrophenyl compounds.

1976 ◽  
Vol 144 (4) ◽  
pp. 1134-1140 ◽  
Author(s):  
T G Rehn ◽  
J K Inman ◽  
G M Shearer
Keyword(s):  
T Cell ◽  
Target Cells ◽  
Cell Recognition ◽  
Receptor Model ◽  
Spleen Cells ◽  
Effector Cells ◽  
T Cell Recognition ◽  
Cytotoxic Effector

The specificity of C57BL/10 cytotoxic effector cells generated by in vitro sensitization with autologous spleen cells modified with a series of related nitrophenyl compounds was investigated. The failure of trinitrophenyl (TNP)-sensitized effector cells to lyse TNP-beta-alanylglycylglycyl(AGG)-modified target cells is presented as evidence contradicting the intimacy or dual receptor model or T-cell recognition in its simplest form. Data are also shown indicating that sensitization with N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-AGG-modified stimulating cells generates noncross-reacting clones of cytotoxic effector cells.

scholarly journals Recognition of virus-infected cells by natural killer cell clones is controlled by polymorphic target cell elements.

1993 ◽  
Vol 178 (3) ◽  
pp. 961-969 ◽  
Author(s):  
M S Malnati ◽  
P Lusso ◽  
E Ciccone ◽  
A Moretta ◽  
L Moretta ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Target Cell ◽  
Nk Cell ◽  
Class I ◽  
Target Cells ◽  
Cell Recognition ◽  
Infected Cells ◽  
Nk Cell Recognition

Natural killer (NK) cells provide a first line of defense against viral infections. The mechanisms by which NK cells recognize and eliminate infected cells are still largely unknown. To test whether target cell elements contribute to NK cell recognition of virus-infected cells, human NK cells were cloned from two unrelated donors and assayed for their ability to kill normal autologous or allogeneic cells before and after infection by human herpesvirus 6 (HHV-6), a T-lymphotropic herpesvirus. Of 132 NK clones isolated from donor 1, all displayed strong cytolytic activity against the NK-sensitive cell line K562, none killed uninfected autologous T cells, and 65 (49%) killed autologous T cells infected with HHV-6. A panel of representative NK clones from donors 1 and 2 was tested on targets obtained from four donors. A wide heterogeneity was observed in the specificity of lysis of infected target cells among the NK clones. Some clones killed none, some killed only one, and others killed more than one of the different HHV-6-infected target cells. Killing of infected targets was not due to complete absence of class I molecules because class I surface levels were only partially affected by HHV-6 infection. Thus, target cell recognition is not controlled by the effector NK cell alone, but also by polymorphic elements on the target cell that restrict NK cell recognition. Furthermore, NK clones from different donors display a variable range of specificities in their recognition of infected target cells.

Dynamic changes in viscoelastic properties in cytotoxic T-lymphocyte-mediated killing

1988 ◽  
Vol 91 (2) ◽  
pp. 179-189 ◽  
Author(s):  
K.L. Sung ◽  
L.A. Sung ◽  
M. Crimmins ◽  
S.J. Burakoff ◽  
S. Chien
Keyword(s):  
T Lymphocyte ◽  
Target Cell ◽  
Viscoelastic Properties ◽  
Cytotoxic T Lymphocyte ◽  
Cell Swelling ◽  
Initial Increase ◽  
Target Cells ◽  
Dynamic Changes ◽  
Lymphocyte Clone ◽  
Membrane Cell

The biophysical properties of cytotoxic T lymphocytes during the killing of their target cells was investigated by using a human cytotoxic T lymphocyte clone, F1, and the target cell, JY, for which it is specific. In single cytotoxic cell/target cell pairs after their conjugation there are changes in the viscoelastic properties of the target cell in association with the lethal hit delivery and post-binding cytolytic steps. On the basis of these changes in the target cell, the complex cytolytic event can be divided into stages: the viscoelastic coefficients exhibited an initial increase followed by a return to resting values; thereafter these coefficients decreased below control and then rose again prior to lysis. The eventual killing of the target cell involves bubbling and swelling of the nucleus, clustering of granules, damage to the cytoplasmic membrane, cell swelling, and lysis. The viscoelastic changes involved in target cell death suggest the loss of integrity of its cytoskeletal apparatus.

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