scholarly journals Sendai Virus Fusion Protein-Mediates Simultaneous Induction of MHC Class I/II-Dependent Mucosal and Systemic Immune Responses Via the Nasopharyngeal-Associated Lymphoreticular Tissue Immune System

2001 ◽  
Vol 167 (3) ◽  
pp. 1406-1412 ◽  
Author(s):  
Jun Kunisawa ◽  
Tsuyoshi Nakanishi ◽  
Ichiro Takahashi ◽  
Akiko Okudaira ◽  
Yasuo Tsutsumi ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Fusion Protein ◽  
Mhc Class I ◽  
Sendai Virus ◽  
Class I ◽  
Virus Fusion ◽  
Simultaneous Induction ◽  
Lymphoreticular Tissue

scholarly journals Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection

2012 ◽  
Vol 6 (2) ◽  
pp. 17 ◽  
Author(s):  
Masachika Senba ◽  
Naoki Mori
Keyword(s):  
Immune Response ◽  
Human Papillomavirus ◽  
Immune System ◽  
Tumor Suppressor ◽  
Chronic Inflammation ◽  
Mhc Class I ◽  
Immune Evasion ◽  
Latency Period ◽  
Class I ◽  
Presentation Pathway

Human papillomavirus (HPV) has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC) class I molecules are patrolled by natural killer cells and CD8<sup>+</sup> cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-kB in cervical and penile cancers suggests that NF-kB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-kB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

scholarly journals Mutation of the TYTLE Motif in the Cytoplasmic Tail of the Sendai Virus Fusion Protein Deeply Affects Viral Assembly and Particle Production

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e78074 ◽  
Author(s):  
Manel Essaidi-Laziosi ◽  
Anastasia Shevtsova ◽  
Denis Gerlier ◽  
Laurent Roux
Keyword(s):  
Fusion Protein ◽  
Particle Production ◽  
Sendai Virus ◽  
Cytoplasmic Tail ◽  
Viral Assembly ◽  
Virus Fusion

DS-8201a, a HER2-targeting antibody-drug conjugate, to elicit immune responses and benefits in combination with an anti-PD-1 antibody.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1031-1031 ◽  
Author(s):  
Tomomi Nakayama Iwata ◽  
Chiaki Ishii ◽  
Yusuke Ogitani ◽  
Teiji Wada ◽  
Toshinori Agatsuma
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Antitumor Efficacy ◽  
Class I ◽  
Antibody Drug Conjugate ◽  
Antitumor Effects ◽  
Drug Conjugate ◽  
Antibody Drug

1031 Background: DS-8201a, a HER2-targeting antibody–drug conjugate (ADC), with a topoisomerase I inhibitor, exatecan drivative (DX-8951 derivative, DXd) has been shown to have antitumor effects in preclinical xenograft models and clinical trials, but the involvement of the immune system in the antitumor efficacy of DS-8201a has not been elucidated yet. Methods: The antitumor efficacy of DS-8201a individually and in combination with an anti-PD-1 antibody was determined in a syngeneic mouse model with human HER2-expressing CT26.WT (CT26.WT-hHER2) cells. Mice whose tumors had been cured by DS-8201a treatment were rechallenged with CT26.WT-hHER2 cells; their splenocytes were co-cultured with CT26.WT-hHER2 or CT26.WT-mock cells, and IFN-g secretion by these cells was determined. To investigate effects of DXd and DS-8201a on dendritic cells (DCs), the expression of DC markers on bone marrow derived DCs (BMDCs) and intratumoral DCs was analyzed by flow cytometry. Furthermore, MHC class I and PD-L1 expression on tumor cells was analyzed. Results: At a weekly dosage of 10 mg/kg, DS-8201a showed significant antitumor effects in the mouse model. Mice whose tumors had been cured by DS-8201a treatment rejected the rechallenge with CT26.WT-hHER2 cells, and splenocytes from these mice were activated by both CT26.WT-hHER2 and CT26.WT-mock cells. In the mouse model, DS-8201a treatment raised a population of intratumoral DCs (CD45+CD11c+MHC class II+) and increased DC expression of CD86, a DC activation marker; DXd also up-regulated CD86 expression on BMDCs in vitro. Furthermore, DS-8201a up-regulated PD-L1 and MHC class I expression on tumor cells. Notably, antitumor effects of the combination of DS-8201a with an anti-PD-1 antibody were better than those of monotherapy. Conclusions: DS-8201a elicits immune responses via mechanisms other than cytotoxic effects on tumor cells. This finding suggests additional benefits of combining DS-8201a with an immune checkpoint inhibitor (ICI). The combination of DS-8201a and an anti-PD-1 antibody was effective in tumor suppression, indicating that DS-8201a may be successfully combined with an ICI in human clinical applications.

NLRC5: a key regulator of MHC class I-dependent immune responses

2012 ◽  
Vol 12 (12) ◽  
pp. 813-820 ◽  
Author(s):  
Koichi S. Kobayashi ◽  
Peter J. van den Elsen
Keyword(s):  
Immune Responses ◽  
Mhc Class I ◽  
Class I

scholarly journals Sequence Determination of the Sendai Virus Fusion Protein Gene

1985 ◽  
Vol 66 (2) ◽  
pp. 317-331 ◽  
Author(s):  
B. M. Blumberg ◽  
C. Giorgi ◽  
K. Rose ◽  
D. Kolakofsky
Keyword(s):  
Fusion Protein ◽  
Protein Gene ◽  
Sendai Virus ◽  
Sequence Determination ◽  
Virus Fusion

scholarly journals Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System

1997 ◽  
Vol 186 (2) ◽  
pp. 209-220 ◽  
Author(s):  
Gabriele Niedermann ◽  
Rudolf Grimm ◽  
Elke Geier ◽  
Martina Maurer ◽  
Claudio Realini ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class I ◽  
Structural Features ◽  
Interferon Γ ◽  
Class I ◽  
Direct Products ◽  
Vertebrate Immune System ◽  
Mhc Class I Molecules

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH2 and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon γ induction in vivo or addition of recombinant proteasome activator 28α in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules.

scholarly journals An Efficient and Versatile Mammalian Viral Vector System for Major Histocompatibility Complex Class I/Peptide Complexes

2002 ◽  
Vol 76 (23) ◽  
pp. 11982-11988 ◽  
Author(s):  
Ai Kawana-Tachikawa ◽  
Mariko Tomizawa ◽  
Jun-ichi Nunoya ◽  
Tatsuo Shioda ◽  
Atsushi Kato ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune Responses ◽  
Mhc Class I ◽  
Class I ◽  
Vector System ◽  
Specific Ctls ◽  
Histocompatibility Complex ◽  
Peptide Complexes ◽  
Hiv 1 ◽  
Made In

ABSTRACT We report a Sendai virus (SeV) vector system for expression of major histocompatibility complex (MHC) class I/peptide complexes. We cloned the extracellular domain of a human MHC class I heavy chain, HLA-A*2402, and human β-2 microglobulin (β2m) fused with HLA-A*2402-restricted human immunodeficiency virus type 1 (HIV-1) cytotoxic T-lymphocyte (CTL) epitopes (e-β2m) in separate SeV vectors. When we coinfected nonhuman mammalian cells with the SeVs, naturally folded human MHC class I/peptide complexes were secreted in the culture supernatants. Biotin binding peptide sequences on the C terminus of the heavy chain were used to tetramerize the complexes. These tetramers made in the SeV system recognized specific CD8-positive T cells in peripheral blood mononuclear cells of HIV-1-positive patients with a specificity and sensitivity similar to those of MHC class I tetramers made in an Escherichia coli system. Solo infection of e-β2m/SeV produced soluble e-β2m in the culture supernatant, and cells pulsed with the soluble protein were recognized by specific CTLs. Furthermore, when cells were infected with e-β2m/SeV, these cells were recognized by the specific CTLs more efficiently than the protein pulse per se. SeV is nonpathogenic for humans, can transduce foreign genes into nondividing cells, and may be useful for immunotherapy to enhance antigen-specific immune responses. Our system can be used not only to detect but also to stimulate antigen-specific cellular immune responses.

scholarly journals Viruses, cancer and non-self recognition

Open Biology ◽  
2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Monikaben Padariya ◽  
Umesh Kalathiya ◽  
Sara Mikac ◽  
Katarzyna Dziubek ◽  
Maria C. Tovar Fernandez ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class I ◽  
Immune Evasion ◽  
Genetic Material ◽  
Class I ◽  
Host Interactions ◽  
Host Interaction ◽  
Self Recognition ◽  
Cancer Mutations ◽  
Cellular Pathways

Virus–host interactions form an essential part of every aspect of life, and this review is aimed at looking at the balance between the host and persistent viruses with a focus on the immune system. The virus–host interaction is like a cat-and-mouse game and viruses have developed ingenious mechanisms to manipulate cellular pathways, most notably the major histocompatibility (MHC) class I pathway, to reside within infected cell while evading detection and destruction by the immune system. However, some of the signals sensing and responding to viral infection are derived from viruses and the fact that certain viruses can prevent the infection of others, highlights a more complex coexistence between the host and the viral microbiota. Viral immune evasion strategies also illustrate that processes whereby cells detect and present non-self genetic material to the immune system are interlinked with other cellular pathways. Immune evasion is a target also for cancer cells and a more detailed look at the interfaces between viral factors and components of the MHC class I peptide-loading complex indicates that these interfaces are also targets for cancer mutations. In terms of the immune checkpoint, however, viral and cancer strategies appear different.

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