scholarly journals Lipid specificity of the immune effector perforin

2020 ◽  
Author(s):  
Adrian W Hodel ◽  
Jesse Rudd-Schmidt ◽  
Joseph A Trapani ◽  
Ilia Voskoboinik ◽  
Bart Hoogenboom
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Immune Effector ◽  
Lymphocyte Membrane ◽  
Infected Cells ◽  
Lipid Specificity

Perforin is a pore forming protein used by cytotoxic T lymphocytes to remove cancerous or virus-infected cells during immune response. During the response, the lymphocyte membrane becomes refractory to perforin...

Caffeine-enhanced anti-tumor immune response through decreased expression of PD1 on infiltrated cytotoxic T lymphocytes

2019 ◽  
Vol 859 ◽  
pp. 172538 ◽  
Author(s):  
Gullanki Naga Venkata Charan Tej ◽  
Kaushik Neogi ◽  
Sumit Singh Verma ◽  
Subash Chandra Gupta ◽  
Prasanta Kumar Nayak
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

scholarly journals Combining PARP inhibition, radiation, and immunotherapy: A possible strategy to improve the treatment of cancer?

2018 ◽  
Vol 19 (12) ◽  
pp. 3793 ◽  
Author(s):  
Mathieu Césaire ◽  
Juliette Thariat ◽  
Serge M. Candéias ◽  
Dinu Stefan ◽  
Yannick Saintigny ◽  
...  
Keyword(s):  
Immune Response ◽  
Radiation Therapy ◽  
T Lymphocytes ◽  
Ionizing Radiation ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Antitumor Immune Response ◽  
Parp Inhibition

Immunotherapy has revolutionized the practice of oncology, improving survival in certain groups of patients with cancer. Immunotherapy can synergize with radiation therapy, increase locoregional control, and have abscopal effects. Combining it with other treatments, such as targeted therapies, is a promising means of improving the efficacy of immunotherapy. Because the value of immunotherapy is amplified with the expression of tumor antigens, coupling poly(ADP-ribose) polymerase (PARP) inhibitors and immunotherapy might be a promising treatment for cancer. Further, PARP inhibitors (PARPis) are being combined with radiation therapy to inhibit DNA repair functions, thus enhancing the effects of radiation; this association might interact with the antitumor immune response. Cytotoxic T lymphocytes are central to the antitumor immune response. PARP inhibitors and ionizing radiation can enhance the infiltration of cytotoxic T lymphocytes into the tumor bed, but they can also enhance PD-1/PDL-1 expression. Thus, the addition of immune checkpoint inhibitors with PARP inhibitors and/or ionizing radiation could counterbalance such immunosuppressive effects. With the present review article, we proposed to evaluate some of these associated therapies, and we explored the biological mechanisms and medical benefits of the potential combination of radiation therapy, immunotherapy, and PARP inhibitors.

scholarly journals Development of a Bioconjugate Platform for Modifying the Immune Response of Autoreactive Cytotoxic T Lymphocytes Involved in Type 1 Diabetes

2019 ◽  
Vol 30 (7) ◽  
pp. 2049-2059 ◽  
Author(s):  
Neha Nandedkar-Kulkarni ◽  
Abhishek R. Vartak ◽  
Steven J. Sucheck ◽  
Katherine A. Wall ◽  
Anthony Quinn ◽  
...  
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

scholarly journals The Hypervariable Immunodominant NP418-426 Epitope from the Influenza A Virus Nucleoprotein Is Recognized by Cytotoxic T Lymphocytes with High Functional Avidity

2006 ◽  
Vol 80 (12) ◽  
pp. 6024-6032 ◽  
Author(s):  
Adrianus C. M. Boon ◽  
Gerrie de Mutsert ◽  
Ron A. M. Fouchier ◽  
Albert D. M. E. Osterhaus ◽  
Guus F. Rimmelzwaan
Keyword(s):  
T Lymphocytes ◽  
Influenza A Virus ◽  
Cytotoxic T Lymphocytes ◽  
Influenza A ◽  
Mononuclear Cells ◽  
Influenza Viruses ◽  
Functional Avidity ◽  
Human Virus ◽  
Ctl Epitopes ◽  
Infected Cells

ABSTRACT Recently it was shown that influenza A viruses can accumulate mutations in epitopes associated with escape from recognition by human virus-specific cytotoxic T lymphocytes (CTL). It is unclear what drives diversification of CTL epitopes and why certain epitopes are variable and others remain conserved. It has been shown that simian immunodeficiency virus-specific CTL that recognize their epitope with high functional avidity eliminate virus-infected cells efficiently and drive diversification of CTL epitopes. T-cell functional avidity is defined by the density of major histocompatibility complex class I peptide complexes required to activate specific CTL. We hypothesized that functional avidity of CTL contributes to epitope diversification and escape from CTL also for influenza viruses. To test this hypothesis, the functional avidity of polyclonal CTL populations specific for nine individual epitopes was determined. To this end, peripheral blood mononuclear cells from HLA-A- and -B-genotyped individuals were stimulated in vitro with influenza virus-infected cells to allow expansion of virus-specific CTL, which were used to determine the functional avidity of CTL specific for nine individual epitopes in enzyme-linked immunospot assays. We found that the functional avidity for the respective epitopes varied widely. Furthermore, the functional avidity of CTL specific for the hypervariable NP418-426 epitope was significantly higher than that of CTL recognizing other epitopes (P < 0.01). It was speculated that the high functional avidity of NP418-426-specific CTL was responsible for the diversification of this influenza A virus CTL epitope.

scholarly journals Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1.

1994 ◽  
Vol 180 (4) ◽  
pp. 1283-1293 ◽  
Author(s):  
T J Tsomides ◽  
A Aldovini ◽  
R P Johnson ◽  
B D Walker ◽  
R A Young ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Cell Lines ◽  
Cytotoxic T Lymphocytes ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

We have established long-term cultures of several cell lines stably and uniformly expressing human immunodeficiency virus type 1 (HIV-1) in order to (a) identify naturally processed HIV-1 peptides recognized by cytotoxic T lymphocytes (CTL) from HIV-1-seropositive individuals and (b) consider the hypothesis that naturally occurring epitope densities on HIV-infected cells may limit their lysis by CTL. Each of two A2-restricted CD8+ CTL specific for HIV-1 gag or reverse transcriptase (RT) recognized a single naturally processed HIV-1 peptide in trifluoroacetic acid (TFA) extracts of infected cells: gag 77-85 (SLYNTVATL) or RT 476-484 (ILKEPVHGV). Both processed peptides match the synthetic peptides that are optimally active in cytotoxicity assays and have the consensus motif described for A2-associated peptides. Their abundances were approximately 400 and approximately 12 molecules per infected Jurkat-A2 cell, respectively. Other synthetic HIV-1 peptides active at subnanomolar concentrations were not present in infected cells. Except for the antigen processing mutant line T2, HIV-infected HLA-A2+ cell lines were specifically lysed by both A2-restricted CTL, although infected Jurkat-A2 cells were lysed more poorly by RT-specific CTL than by gag-specific CTL, suggesting that low cell surface density of a natural peptide may limit the effectiveness of some HIV-specific CTL despite their vigorous activity against synthetic peptide-treated target cells.

scholarly journals RMA/S cells present endogenously synthesized cytosolic proteins to class I-restricted cytotoxic T lymphocytes.

1992 ◽  
Vol 175 (1) ◽  
pp. 163-168 ◽  
Author(s):  
F Esquivel ◽  
J Yewdell ◽  
J Bennink
Keyword(s):  
T Lymphocytes ◽  
Cell Surface ◽  
Cytotoxic T Lymphocytes ◽  
Antigen Processing ◽  
Mutant Cell ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Antigenic Peptides ◽  
Infected Cells

RMA/S is a mutant cell line with decreased cell surface expression of major histocompatibility complex class I molecules that has been reported to be deficient in presenting endogenously synthesized influenza virus nucleoprotein (NP) to cytotoxic T lymphocytes (CTL). In the present study we show that RMA/S cells can present vesicular stomatitis virus nucleocapsid protein, and, under some conditions, NP, to Kb-and Db-restricted CTL, respectively. Antigen presentation results from processing of cytosolic pools of endogenously synthesized proteins, and not the binding to cell surface class I molecules of antigenic peptides present in the virus inoculum or released from infected cells. Antigen processing of RMA/S differs, however, from processing by wild-type cells in requiring greater amounts of antigen, longer times to assemble or transport class I-peptide complexes, and in being more sensitive to blocking by anti-CD8 antibody. Thus, the antigen processing deficit in RMA/S cells is of a partial rather than absolute nature.

The advantage of early recognition of HIV-infected cells by cytotoxic T-lymphocytes

Vaccine ◽  
2002 ◽  
Vol 20 (15) ◽  
pp. 2011-2015 ◽  
Author(s):  
Rob A Gruters ◽  
Carel A van Baalen ◽  
Albert D.M.E Osterhaus
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Early Recognition ◽  
Infected Cells
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