Faculty Opinions recommendation of Modified vaccinia virus Ankara-infected dendritic cells present CD4+ T-cell epitopes by endogenous major histocompatibility complex class II presentation pathways.

2015 ◽  
Author(s):  
Christian Münz
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Vaccinia Virus ◽  
Major Histocompatibility Complex Class ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Complex Class ◽  
Histocompatibility Complex ◽  
Modified Vaccinia Virus Ankara

Immuno-informatics-based identification of novel potential B cell and T cell epitopes to fight Zika virus infections

2020 ◽  
Vol 20 ◽  
Author(s):  
Wahiba Ezzemani ◽  
Marc P. Windisch ◽  
Anass Kettani ◽  
Haya Altawalah ◽  
Jalal Nourlil ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
B Cell ◽  
Zika Virus ◽  
T Cell Epitopes ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Virus Infections ◽  
Histocompatibility Complex

Background: Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. Objective: In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. Methods: The prediction of the most antigenic epitopes has targeted the capsid and the envelope proteins as well as nonstructural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity were evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss-Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. Results: As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68 :01), ETLHGTVTV (HLA-A*68 :02), DENHPYRTW (HLA-B*44 :02),QEGVFHTMW (HLA-B*44 :03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02 :02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAETWFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11 :01), and DGCWYGMEIRPRKEP (HLA-DRB5*01:01). Conclusion : This study provides novel potential B cell and T cell epitopes to fight Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify the immunogenicity, safety of the predicted structure, and ultimately the vaccine properties to prevent ZIKV infections are warranted.

scholarly journals Selective enrichment of major histocompatibility complex class II-specific autoreactive T cells in the thymic Thy0 subset.

1993 ◽  
Vol 177 (5) ◽  
pp. 1429-1437 ◽  
Author(s):  
I Kariv ◽  
R R Hardy ◽  
K Hayakawa
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Complex Class ◽  
Autoreactive T Cells ◽  
Cell Hybrids ◽  
Histocompatibility Complex

We show here a unique enrichment of autoreactive T cells in the CD4+ mouse thymic subset, Thy0. A single- and 10-cell AMLR (autologous mixed leukocyte reaction) assay demonstrates that more than 30% (one cell per well) and almost all (10 cells per well) Thy0 cultures from normal mice exhibit reactivity specific to autologous cells, resulting in induction of interleukin 3 secretion. In contrast, no other mature thymic or splenic CD4+ T cell subsets showed such a high frequency. The majority of this AMLR reactivity in the Thy0 subset is accounted for by reactivity with self-major histocompatibility complex class II. Furthermore, antigenic selection in generating Thy0 subset is suggested by studies with T cell hybrids from a T cell receptor (TCR) V beta transgenic mouse line, 2B4 beta EH. TCR V-gene analysis of T cell hybrids revealed that those from Thy0, half of which responded to self-class II, consisted predominantly of cells that expressed endogenous TCR V beta s alone (without the transgene), unlike hybrids generated from peripheral naive T cells. Thus, we suggest that the presence of Thy0 results from selective stimulation of cells expressing TCR with sufficient affinity for autoantigens in the thymic CD4+ T cell repertoire.

scholarly journals Pol-Specific CD8+ T Cells Recognize Simian Immunodeficiency Virus-Infected Cells Prior to Nef-Mediated Major Histocompatibility Complex Class I Downregulation

2007 ◽  
Vol 81 (21) ◽  
pp. 11703-11712 ◽  
Author(s):  
Jonah B. Sacha ◽  
Chungwon Chung ◽  
Jason Reed ◽  
Anna K. Jonas ◽  
Alexander T. Bean ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
T Cell Epitopes ◽  
Complex Class ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Infected Cells

ABSTRACT Effective, vaccine-induced CD8+ T-cell responses should recognize infected cells early enough to prevent production of progeny virions. We have recently shown that Gag-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells at 2 h postinfection, whereas Env-specific CD8+ T cells do not recognize infected cells until much later in infection. However, it remains unknown when other proteins present in the viral particle are presented to CD8+ T cells after infection. To address this issue, we explored CD8+ T-cell recognition of epitopes derived from two other relatively large virion proteins, Pol and Nef. Surprisingly, infected cells efficiently presented CD8+ T-cell epitopes from virion-derived Pol proteins within 2 h of infection. In contrast, Nef-specific CD8+ T cells did not recognize infected cells until 12 h postinfection. Additionally, we show that SIVmac239 Nef downregulated surface major histocompatibility complex class I (MHC-I) molecules beginning at 12 h postinfection, concomitant with presentation of Nef-derived CD8+ T-cell epitopes. Finally, Pol-specific CD8+ T cells eliminated infected cells as early as 6 h postinfection, well before MHC-I downregulation, suggesting a previously underappreciated antiviral role for Pol-specific CD8+ T cells.

CD4+ T cell-mediated rejection of major histocompatibility complex class I-disparate grafts: A role for alloantibody

1993 ◽  
Vol 23 (9) ◽  
pp. 2078-2084 ◽  
Author(s):  
A. Lawrie Morton ◽  
Eric B. Bell ◽  
Eleanor M. Bolton ◽  
Hilary E. Marshall ◽  
Chris Roadknight ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Cd4 T Cell ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

scholarly journals Treatment of a glioblastoma patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I–matched tumor peptides

2000 ◽  
Vol 9 (6) ◽  
pp. 1-5 ◽  
Author(s):  
Linda M. Liau ◽  
Keith L. Black ◽  
Neil A. Martin ◽  
Steven N. Sykes ◽  
Jeff M. Bronstein ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Immune Responses ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Outpatient Basis ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Dendritic cells (DCs) are antigen-presenting cells that play a central role in the initiation and modulation of antitumor immune responses. In this pilot study, we investigated the ability of autologous DCs pulsed ex vivo with allogeneic major histocompatibility complex class I–matched glioblastoma peptides to stimulate host antitumor immune responses when injected as a vaccine. A patient with recurrent brainstem glioblastoma multiforme (GBM) received a series of three intradermal immunizations of antigen-pulsed DCs on an outpatient basis following surgical debulking of her posterior fossa tumor. Dendritic cell vaccination was well tolerated, and no clinical signs of autoimmunity or experimental allergic en-cephalomyelitis were detected. She developed a measurable cellular immune response against the allogeneic glioblastoma peptides used in her vaccine preparation, as demonstrated by in vitro T-cell proliferation assays. In addition, increased T-cell infiltration was noted within the intracranial tumor site in the biopsy sample obtained following DC vaccination. An objective clinical response, however, was not evident, and this patient eventually died 21 months after her disease was diagnosed. To our knowledge, this is the first patient with brain cancer ever to be treated with DC-based immunotherapy. This case illustrates that vaccination with DCs pulsed with acid-eluted glioblastoma peptides is feasible and can induce systemic antigen-specific immunity in a patient with recurrent GBM. Additional studies are necessary to determine the optimum DC doses and antigen loading conditions that may translate into clinical effectiveness and survival benefit for patients with brain tumors. Phase I trials for malignant glioma are currently underway.

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