scholarly journals In-silico Immunomodelling of 2019-nCoV

2020 ◽  
Author(s):  
Amirhosein Maali ◽  
Hossein Teimouri ◽  
Shahin Amiri ◽  
Setare Adibzadeh ◽  
Mehdi Azad
Keyword(s):  
B Cell ◽  
Mhc Class I ◽  
Cellular Immunity ◽  
Rna Virus ◽  
Class I ◽  
Cleavage Pattern ◽  
T Cell Epitopes ◽  
Corona Virus ◽  
Anti Inflammatory ◽  
Proteasomal Cleavage

Abstract Background: Novel Corona Virus 2019 (2019-nCoV) is a positive-sense single-strand RNA virus form coronaviridae family, responsible for corona virus infectious disease 2019 (COVID-19) with rapid transmission. The aim of this study is characterization of major viral proteins, prediction of antigen proteasomal cleavage pattern, MHC class I processing and presentation, B- and T-cell epitopes, and anti-inflammatory epitopes of 2019-nCoV, compared with SARS-CoV. Methods: The aminoacid sequence of spike surface (S) glycoprotein, membrane (M) glycoprotein, envelop (E) protein and nucleocapsid (N) phosphoprotein were obtained from NCBI. The sequences were aligned by MEGA 7.0 and modeled by SWISS-MODEL. The proteasomal cleavage pattern, MHC class I processing and T-cells epitopes were predicted via IEDB analysis and EPISOFT. The B-cell epitopes were predicted by BepiPred 2.0. Also, prediction of anti-inflammatory epitopes was performed by AntiFlam. Results: Two major antigen proteins, S glycoprotein and M glycoprotein of 2019-nCoV, respectively, have 26.57% and 20.59% less efficiency in proteasomal cleavage and presentation to MHC class I, comparing SARS-CoV. There are less B-cell predicted epitopes in 2019-nCoV, comparing SARS-CoV. The anti-inflammatory properties of 2019-nCoV S glycoprotein and N protein is higher than SARS-CoV. Discussion: It seems that the evolution of 2019-nCoV is on the way of deficiency in antigen presenting to MHC class I and escaping from cellular immunity. Also, the predicted hotspot epitopes potentially can be used to induction of adaptive cellular immunity against 2019-nCoV. In addition, 2019-nCoV appears to be less immunopathogenic than SARS-CoV due to its higher anti-inflammatory proteins.

Novel epitope based peptides for vaccine against SARS-CoV-2 virus: immunoinformatics with docking approach

2020 ◽  
Vol 8 (7) ◽  
pp. 2385 ◽  
Author(s):  
Jesvin Bency B. ◽  
Mary Helen P. A.
Keyword(s):  
B Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Peptide Vaccine ◽  
Human Leukocyte ◽  
Respiratory Illness ◽  
Class Ii ◽  
Class I ◽  
T Cell Epitopes ◽  
B Cell Epitopes

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative viral strain for the contagious pandemic respiratory illness in humans which is a public health emergency of international concern. There is a desperate need for vaccines and antiviral strategies to combat the rapid spread of SARS-CoV-2 infection.Methods: The present study based on computational methods has identified novel conserved cytotoxic T-lymphocyte epitopes as well as linear and discontinuous B-cell epitopes on the SARS-CoV-2 spike (S) protein. The predicted MHC class I and class II binding peptides were further checked for their antigenic scores, allergenicity, toxicity, digesting enzymes and mutation.Results: A total of fourteen linear B-cell epitopes where GQSKRVDFC displayed the highest antigenicity-score and sixteen highly antigenic 100% conserved T-cell epitopes including the most potential vaccine candidates MHC class-I peptide KIADYNYKL and MHC class-II peptide VVFLHVTYV were identified. Furthermore, the potential peptide QGFSALEPL with high antigenicity score attached to larger number of human leukocyte antigen alleles. Docking analyses of the allele HLA-B*5201 predicted to be immunogenic to several of the selected epitopes revealed that the peptides engaged in strong binding with the HLA-B*5201 allele.Conclusions: Collectively, this research provides novel candidates for epitope-based peptide vaccine design against SARS-CoV-2 infection.

scholarly journals Structural modeling and conserved epitopes prediction against SARS-COV-2 structural proteins for vaccine development

2020 ◽  
Author(s):  
Muhammad Tahir ul Qamar ◽  
Farah Shahid ◽  
Usman Ali Ashfaq ◽  
Sidra Aslam ◽  
Israr Fatima ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Structural Proteins ◽  
Severe Illness ◽  
T Cell Epitopes ◽  
B Cell Epitopes

Abstract Background: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona virus 2 (SARS-COV-2) was first diagnosed in December 2019, Wuhan, China. Little is known about this new virus and it has the potential to cause severe illness and pneumonia in some people, therefore the development of an effective vaccine is highly desired.Methods: Immunoinformatics and statistical approaches were used in this study to forecast B- and T- cell epitopes for the SARS-COV-2 structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) that may play a key role in eliciting immune response against COVID-19. Different types of B cell epitopes (linear as well as discontinuous) and T cell (MHC class I and MHC class II) were determined. Moreover, their antigenicity and allergenicity were also estimated.Results: The antigenic B-cell epitopes exposed to the outer surface were screened out and 23 linear B cell epitopes were selected. “SPTKLNDLCFTNVY” had the highest antigenicity score among B cell epitopes. The T-cell epitopes bound to multiple alleles, antigenic, non-allergen, non-toxic, and conserved in the protein sequence were shortlisted. In total, 16 epitopes (9 from MHC class I and 7 from MHC class II) were selected. Among the T-cell epitopes, MHC class I (IPFAMQMAYRFN) and MHC class II (VTLACFVLAAVYRIN) were classified as strongly antigenic. Digestion analysis verified the safety and stability of the peptides predicted during this study. Furthermore, docking analyses of predicted peptides showed significant interactions with the HLA-B7 allele.Conclusion: The putative antigen epitopes identified in this study may serve as vaccine candidates and can help to eliminate/control growing health threat of COVID-19.

T-cell epitopes within the complementarity-determining and framework regions of the tumor-derived immunoglobulin heavy chain in multiple myeloma

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4930-4936 ◽  
Author(s):  
Lotta Hansson ◽  
Hodjattallah Rabbani ◽  
Jan Fagerberg ◽  
Anders Österborg ◽  
Håkan Mellstedt
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Heavy Chain ◽  
T Cell Response ◽  
Class I ◽  
Type I ◽  
T Cell Epitopes ◽  
Hla Binding

Abstract The idiotypic structure of the monoclonal immunoglobulin (Ig) in multiple myeloma (MM) might be regarded as a tumor-specific antigen. The present study was designed to identify T-cell epitopes of the variable region of the Ig heavy chain (VH) in MM (n = 5) using bioinformatics and analyze the presence of naturally occurring T cells against idiotype-derived peptides. A large number of human-leukocyte-antigen (HLA)–binding (class I and II) peptides were identified. The frequency of predicted epitopes depended on the database used: 245 in bioinformatics and molecular analysis section (BIMAS) and 601 in SYFPEITHI. Most of the peptides displayed a binding half-life or score in the low or intermediate affinity range. The majority of the predicted peptides were complementarity-determining region (CDR)–rather than framework region (FR)–derived (52%-60% vs 40%-48%, respectively). Most of the predicted peptides were confined to the CDR2-FR3-CDR3 “geographic” region of the Ig-VH region (70%), and significantly fewer peptides were found within the flanking (FR1-CDR1-FR2 and FR4) regions (P < .01). There were 8– to 10–amino acid (aa) long peptides corresponding to the CDRs and fitting to the actual HLA-A/B haplotypes that spontaneously recognized, albeit with a low magnitude, type I T cells (interferon γ), indicating an ongoing major histocompatibility complex (MHC) class I–restricted T-cell response. Most of those peptides had a low binding half-life (BIMAS) and a low/intermediate score (SYFPEITHI). Furthermore, 15- to 20-aa long CDR1-3–derived peptides also spontaneously recognized type I T cells, indicating the presence of MHC class II–restricted T cells as well. This study demonstrates that a large number of HLA-binding idiotypic peptides can be identified in patients with MM. Such peptides may spontaneously induce a type I MHC class I– as well as class II–restricted memory T-cell response.

Identification of SIV Nef CD8+ T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model

2014 ◽  
Vol 450 (2) ◽  
pp. 942-947 ◽  
Author(s):  
Takushi Nomura ◽  
Hiroyuki Yamamoto ◽  
Naofumi Takahashi ◽  
Taeko K. Naruse ◽  
Akinori Kimura ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Cd8 T Cell ◽  
Class I ◽  
T Cell Epitopes ◽  
Aids Model ◽  
Viral Loads ◽  
Macaque Aids Model

scholarly journals Characterization of MHC class I alleles in sooty mangabeys as a tool for evaluating cellular immunity in natural hosts of SIV infection

2015 ◽  
Vol 67 (8) ◽  
pp. 447-461 ◽  
Author(s):  
Zichun Wang ◽  
Benjamin Metcalf ◽  
Melissa Kasheta ◽  
Caitlin Kasala-Hallinan ◽  
Dollnovan Tran ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Cellular Immunity ◽  
Class I ◽  
Sooty Mangabeys ◽  
Natural Hosts ◽  
Siv Infection

Predicting promiscuous antigenic T cell epitopes of Mycobacterium tuberculosis mymA operon proteins binding to MHC Class I and Class II molecules

2016 ◽  
Vol 44 ◽  
pp. 182-189 ◽  
Author(s):  
Iti Saraav ◽  
Kirti Pandey ◽  
Monika Sharma ◽  
Swati Singh ◽  
Prasun Dutta ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Mhc Class I ◽  
Class Ii ◽  
Class I ◽  
T Cell Epitopes

Non-Cognate Cytotoxic T Cells Can Be Retargeted Against CD20 Positive Tumour Cells Using [Fab' × MHC Class I/Peptide] Conjugates.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2838-2838
Author(s):  
Angela D Hamblin ◽  
Ben CR King ◽  
Ruth R French ◽  
Claude H Chan ◽  
Alison L Tutt ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Mhc Class I ◽  
Peripheral Blood ◽  
Class I ◽  
B Cell Depletion ◽  
Cytokine Release ◽  
Anti Cd20

Abstract Abstract 2838 To circumvent cytotoxic T lymphocyte (CTL) tolerance of tumour-associated antigens, the concept of redirecting CTLs against non-cognate targets has developed. One way of doing this is to use bispecific antibodies comprising anti-CD3 and anti-tumour antigen moieties. Unfortunately, this is frequently associated with unacceptable toxicity due to inflammatory cytokine release. As an alternative our approach has been to use a bivalent conjugate recognising a tumour antigen (through an antibody fragment) and a defined population of CTLs (specific for a single antigenic peptide e.g. viral epitope) through peptide presented in the context of recombinant MHC class I. We have produced a conjugate consisting of an anti-human CD20 Fab' fragment joined via a chemical crosslinker (succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate) to murine MHC class I/peptide (Kbα1-α3 domains/β2microglobulin presenting the ovalbumin-derived peptide SIINFEKL; expressed bacterially as a continuous polypeptide single chain trimer after Yu et al, J Immunol 2002). Size exclusion chromatography allowed purification of conjugates with [Fab':MHC class I/peptide] ratios of 1:1 and 2:1 (F2 and F3 respectively). In vitro both constructs were able to redirect the transgenic murine CTL line OT-1 (specific for KbSIINFEKL) to lyse human CD20+ tumour cells (lymphoblastoid Daudi cell line) at effector: target ratios of 10:1. This lysis could be blocked by the addition of 100 fold excess of either anti-CD20 F(ab')2 or the Kb/SIINFEKL-specific antibody 25D1. The constructs were also able to cause in vitro proliferation of naïve OT-1 cells (but not irrelevant CD8+ T cells) in the presence of human CD20+ cells in both thymidine incorporation and CFSE dilution assays. Using a human CD20 transgenic mouse model (Ahuja et al, J Immunol 2007) we have evaluated both constructs in vivo for their ability to redirect adoptively transferred OT-1 cells to deplete B cells from the peripheral blood. A single dose of 1 nmole F3 and 2 nmole F2 caused respectively up to 95% and 85% B cell depletion at day 7. The efficacy of lower doses suggested a dose: response relationship. As a marker of toxicity, we have measured cytokine levels at 2, 8 and 24 hours following a dose of 1 nmole F3 and compared them to those seen after administration of an [anti-CD3 × anti-CD20] bispecific F(ab')2 at a dose (0.5 nmole) which produced similar day 7 peripheral blood B cell depletion: phosphate-buffered saline was given as a negative control. Maximal cytokine release was seen at 2 hours with the levels of IL-4, IL-5, KC, IL-2 and IL-10 being lower after administration of the F3 than after the bispecific F(ab')2. However, interestingly, the F3 resulted in greater IL-12 release. Overall these data suggest that [Fab' × MHC class I/peptide] constructs have the potential to redirect non-cognate CTLs to deplete CD20+ malignant B cells from the peripheral blood and that this is associated with a lower level of cytokine release than a similarly efficacious dose of an anti-CD3-containing bispecific F(ab')2. Furthermore, the ability of [Fab' × MHC class I/peptide] constructs to cause proliferation of OT-1 cells in vitro suggests it may be possible to use a single molecule to both generate a secondary cytotoxic T cell response and subsequently to retarget it, increasing the viability of the approach if adopted in the clinic. Disclosures: No relevant conflicts of interest to declare.

Evaluation of T-cell responses to peptides with MHC class I-binding motifs derived from PE_PGRS 33 protein of Mycobacterium tuberculosis

2007 ◽  
Vol 56 (4) ◽  
pp. 466-474 ◽  
Author(s):  
M. G. Chaitra ◽  
M. S. Shaila ◽  
R. Nayak
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Mhc Class I ◽  
Class I ◽  
Interleukin 4 ◽  
Specific Response ◽  
T Cell Epitopes ◽  
Cytotoxic Lymphocyte ◽  
Cell Responses ◽  
High Affinity

The PE and PPE proteins of Mycobacterium tuberculosis form a source of antigenic variation among different strains of M. tuberculosis. One of the PE_PGRS proteins, Rv1818c, plays a role in the pathogenesis of mycobacterial infection and specifically influences host-cell responses to tuberculosis infection. Although little is known about these two classes of protein, an immunoinformatics approach has indicated the possibility of their participation in eliciting a major histocompatibility complex (MHC) class I-mediated immune response against tuberculosis, as peptides derived from Rv1818c are predicted to bind to MHC class I molecules with high affinity. In the present work, a DNA vaccine was constructed encoding the full-length Rv1818c protein of M. tuberculosis and its immunogenicity was analysed in BALB/c mice. Immunization with Rv1818c DNA induced a strong CD8+ cytotoxic lymphocyte and Th1-type response, with high levels of gamma interferon (IFN-γ) and low levels of interleukin-4. Two nonameric peptides (Peptide6–14 and Peptide385–393) from Rv1818c were identified by their ability to induce the production of IFN-γ by CD8+ T cells in mice immunized with Rv1818c DNA. An epitope-specific response was demonstrated by the lysis of peptide-pulsed antigen-presenting cells, release of cytotoxic granules and IFN-γ production. These peptides bound with high affinity to MHC H-2Kd and showed low dissociation rates of peptide–MHC complexes. These results could form the basis for testing the identified T-cell epitopes of PE_PGRS proteins in the induction of protective immunity against M. tuberculosis challenge in the mouse model.

Sign in / Sign up

Export Citation Format

Share Document