scholarly journals Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Retrovirology ◽  
2014 ◽  
Vol 11 (1) ◽  
Author(s):  
Aileen G Rowan ◽  
Koichiro Suemori ◽  
Hiroshi Fujiwara ◽  
Masaki Yasukawa ◽  
Yuetsu Tanaka ◽  
...  
Keyword(s):  
Protein Expression ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Infected Cells

scholarly journals Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo

PLoS Biology ◽  
2006 ◽  
Vol 4 (4) ◽  
pp. e90 ◽  
Author(s):  
Becca Asquith ◽  
Charles T. T Edwards ◽  
Marc Lipsitch ◽  
Angela R McLean
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Enhanced Intracellular Dissociation of Major Histocompatibility Complex Class I–associated Peptides: A Mechanism for Optimizing the Spectrum of Cell Surface–Presented Cytotoxic T Lymphocyte Epitopes

1997 ◽  
Vol 185 (8) ◽  
pp. 1403-1412 ◽  
Author(s):  
Alice J.A.M. Sijts ◽  
Eric G. Pamer
Keyword(s):  
Endoplasmic Reticulum ◽  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Half Life ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Mhc Class I Molecules

Association of antigenic peptides with newly synthesized major histocompatibility complex (MHC) class I molecules occurs in the endoplasmic reticulum and is a critical early step for the initiation of cytotoxic T lymphocyte (CTL)-mediated immune defenses. Pathogen-derived peptides compete with a plethora of endogenous peptides for MHC class I grooves. We find that two H2-Kd–restricted peptides, which derive from the Listeria monocytogenes p60 antigen, accumulate in infected cells with different kinetics. Although competition assays suggest that both epitopes are bound with equivalent affinity, they dissociate from MHC class I molecules at markedly different rates. p60 217-225 forms complexes with H2-Kd with a half-life >6 h, while p60 449-457 dissociates from H2-Kd with a half-life of ∼1 h. We find that p60 449-457–H2-Kd complexes retained intracellularly with brefeldin A have a half-life of 30 min, and thus are less stable than surface complexes. While peptide dissociation from retained MHC class I molecules is enhanced, retained H2-Kd molecules maintain a remarkable capacity to bind new T cell epitopes. We find that intracellular H2-Kd molecules can bind new CTL epitopes for up to 3 h after their synthesis. Our studies provide a glimpse of peptide interaction with MHC class I molecules in the endoplasmic reticulum/proximal Golgi complex of intact, infected cells. We propose that the increased intracellular lability of peptide–MHC class I complexes may function to optimize the spectrum of peptides presented to T lymphocytes during cellular infection.

Cytotoxic T lymphocyte recognition of HLA-B*5101-restricted HIV-1 Rev epitope which is naturally processed in HIV-1-infected cells

AIDS ◽  
1999 ◽  
Vol 13 (7) ◽  
pp. 861 ◽  
Author(s):  
Hiroko Tomiyama ◽  
Yoshitomo Chujoh ◽  
Tatsuo Shioda ◽  
Kiyoshi Miwa ◽  
Shin-ichi Oka ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Evaluation of CD8 T cell killing models with computer simulations of 2-photon imaging experiments

2019 ◽  
Author(s):  
Ananya Rastogi ◽  
Philippe Robert ◽  
Stephan Halle ◽  
Michael Meyer-Hermann
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cytotoxic T Cells ◽  
Signal Integration ◽  
Agent Based ◽  
Killing Activity ◽  
Infected Cells

AbstractIn vivo imaging of cytotoxic T lymphocyte (CTL) killing activity revealed that infected cells have a higher observed probability of dying after multiple contacts with CTLs, suggesting memory effect in CTLs or infected cells. We developed a three-dimensional agent-based model of CTL killing activity to discriminate different hypotheses about how infected cells get killed based on quantitative 2-photon in vivo observations. We compared a constant CTL killing probability with mechanisms of signal integration in CTL or infected cells. The most likely scenario implied increased susceptibility of infected cells with increasing number of CTL contacts where the total number of contacts was a critical factor as opposed to signal integration over many contacts. However, when allowing in silico T cells to interact with apoptotic target cells (zombie contacts), a contact history independent killing mechanism was also in agreement with the experimental datasets. We showed that contacts that take place between CTLs and dying infected cells impact the observed killing dynamics because even in absence of modulation of cell properties, we saw an increase of the observed probability of killing infected cells with more interactions. The duration taken by an infected cell to die and the per capita killing rate (PCKR) of CTLs, parameters hard to measure directly, were determined from the model and turned out predictive to distinguish the different CTL killing models in future experiments. The comparison of observed datasets to simulation results, revealed limitations in interpreting 2-photon data, and provided prediction for additional measurements to distinguish CTL killing models.HighlightsKilling of infected cells by cytotoxic T cells typically involves more than a single contact.Cytotoxic T cells or infected cells integrate signals from multiple interactions.T cell contacts with dying infected cells have a major impact on in vivo data interpretation.Significance StatementDespite having a clear understanding of cytotoxic T lymphocyte (CTL) mediated cytotoxicity mechanisms, the quantitative dynamics remain unexplored at a cellular level. We developed an agent-based model to compare different hypotheses for mechanisms of CTL mediated cytotoxicity that could lead to an increase in observed probability of killing infected cells at higher interactions with CTLs as seen in vivo. We showed that this behaviour can be explained by modulation of properties by infected cells or CTLs with increasing number of contacts. For the modulation, we compared two modes of signal integration and showed that time is not a relevant parameter in signal integration. We also studied the impact of contacts between CTLs and apoptotic infected cells on observed killing properties.

scholarly journals P12.06 Clinicopathological evaluation of PD-L1 expression and cytotoxic T-lymphocyte infiltrates across intracranial molecular subgroups of ependymomas

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii60-iii60
Author(s):  
A Sharma
Keyword(s):  
Protein Expression ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Molecular Subgroups ◽  
Chromosome 1Q ◽  
Not Otherwise Specified ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Grade Ii ◽  
L1 Protein

Abstract BACKGROUND Immune check-point blockade targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in the treatment of advanced cancer. The prognosis of the ‘ST-RELA’ and ‘PF-A’ molecular subgroups of ependymomas (EPN) remains poor. This study aims to understand the potential candidature of EPNs for ICB. MATERIAL AND METHODS All supratentorial (ST) Grade II/III EPNs were classified into ST-RELA, ST-YAP and ST-not otherwise specified (NOS), based on L1CAM protein expression and/or presence of RELA/YAP1 fusion transcripts by RT-PCR. All posterior fossa (PF) BEPNs were classified into PF-A and PF-B based on H3K27me3 protein expression and chromosome 1q gain. Immunohistochemistry for PD-L1 (SP263, Ventana) and CD8 was performed. RelA protein enrichment at PDL1 promoter site was analysed by chromatin immunoprecipitation-qPCR (ChIP-qPCR) in three ST-RELA samples. RESULTS A total of 83 intracranial EPNs were included as follows: ST-RELA (n=32), ST-YAP (n=1), ST-NOS (n=11), ST-subependymoma (n=1), PF-A (n=25) and PF-B (n=13). Median tumor infiltrating CD8+ cytotoxic T-lymphocyte (CTL) density was 6/mm2, and was higher in ST EPNs (median 10/mm2) as compared to PF EPNs (median 3/mm2). PD-L1 protein expression in ≥1% tumor cells was noted in 17/83 (20%) of all EPNs, including 12/32 (37%) of ST-RELA and rare ST-NOS (2/11), PF-A (2/25) and PF-B (1/13) tumors. Twelve intracranial EPNs (14%, 12/83) showed high CTL density and concurrent PD-L1 positivity, of which majority (83%, 10/12) were ST-RELA EPNs. Enrichment of RelA protein was seen at PD-L1 promoter. CONCLUSION Increased CTL densities and upregulation of PD-L1 in ST-RELA ependymomas suggests potential candidature for immunotherapy.

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