scholarly journals NetMHCpan 4.0: Improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data

2017 ◽  
Author(s):  
Vanessa Jurtz ◽  
Sinu Paul ◽  
Massimo Andreatta ◽  
Paolo Marcatili ◽  
Bjoern Peters ◽  
...  
Keyword(s):  
T Cell ◽  
Binding Affinity ◽  
Large Scale ◽  
Peptide Binding ◽  
Length Distribution ◽  
Class I ◽  
T Cell Epitopes ◽  
Data Types ◽  
Mhc Molecules ◽  
Presentation Pathway

AbstractCytotoxic T cells are of central importance in the immune system’s response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC (major histocompatibility complex) class I molecules. Peptide binding to MHC molecules is the single most selective step in the antigen presentation pathway. On the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has therefore attracted large attention.In the past, predictors of peptide-MHC interaction have in most cases been trained on binding affinity data. Recently an increasing amount of MHC presented peptides identified by mass spectrometry has been published containing information about peptide processing steps in the presentation pathway and the length distribution of naturally presented peptides. Here, we present NetMHCpan-4.0, a method trained on both binding affinity and eluted ligand data leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an increased predictive performance compared to state-of-the-art when it comes to identification of naturally processed ligands, cancer neoantigens, and T cell epitopes.

Synthetic peptide libraries in the determination of T cell epitopes and peptide binding specificity of class I molecules

1992 ◽  
Vol 22 (6) ◽  
pp. 1405-1412 ◽  
Author(s):  
Ton N. M. Schumacher ◽  
Grada M. Van Bleek ◽  
Marie-ThéRèSe Heemels ◽  
Karl Deres ◽  
Ka Wan Li ◽  
...  
Keyword(s):  
T Cell ◽  
Synthetic Peptide ◽  
Peptide Binding ◽  
Binding Specificity ◽  
Peptide Libraries ◽  
Class I ◽  
T Cell Epitopes ◽  
Peptide Binding Specificity

scholarly journals Flow cytometric analysis of peptide binding to major histocampatibility complex class I for hepatitis C virus core T-cell epitopes

Cytometry ◽  
2000 ◽  
Vol 41 (4) ◽  
pp. 271-278 ◽  
Author(s):  
Susann Schweitzer ◽  
Angelika M. Schneiders ◽  
Bettina Langhans ◽  
Wolfgang Kraas ◽  
G�nther Jung ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Peptide Binding ◽  
Flow Cytometric Analysis ◽  
Class I ◽  
T Cell Epitopes ◽  
Complex Class ◽  
Virus Core ◽  
Flow Cytometric

scholarly journals NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data

2020 ◽  
Vol 48 (W1) ◽  
pp. W449-W454 ◽  
Author(s):  
Birkir Reynisson ◽  
Bruno Alvarez ◽  
Sinu Paul ◽  
Bjoern Peters ◽  
Morten Nielsen
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Antigenic Peptides ◽  
Data Types ◽  
Binding Prediction ◽  
Class I Mhc ◽  
Mhc I ◽  
Mhc Molecules ◽  
Mhc Ii ◽  
Presentation Pathway

Abstract Major histocompatibility complex (MHC) molecules are expressed on the cell surface, where they present peptides to T cells, which gives them a key role in the development of T-cell immune responses. MHC molecules come in two main variants: MHC Class I (MHC-I) and MHC Class II (MHC-II). MHC-I predominantly present peptides derived from intracellular proteins, whereas MHC-II predominantly presents peptides from extracellular proteins. In both cases, the binding between MHC and antigenic peptides is the most selective step in the antigen presentation pathway. Therefore, the prediction of peptide binding to MHC is a powerful utility to predict the possible specificity of a T-cell immune response. Commonly MHC binding prediction tools are trained on binding affinity or mass spectrometry-eluted ligands. Recent studies have however demonstrated how the integration of both data types can boost predictive performances. Inspired by this, we here present NetMHCpan-4.1 and NetMHCIIpan-4.0, two web servers created to predict binding between peptides and MHC-I and MHC-II, respectively. Both methods exploit tailored machine learning strategies to integrate different training data types, resulting in state-of-the-art performance and outperforming their competitors. The servers are available at http://www.cbs.dtu.dk/services/NetMHCpan-4.1/ and http://www.cbs.dtu.dk/services/NetMHCIIpan-4.0/.

scholarly journals Delivery of CD8+ T-Cell Epitopes into Major Histocompatibility Complex Class I Antigen Presentation Pathway by Bordetella pertussis Adenylate Cyclase: Delineation of Cell Invasive Structures and Permissive Insertion Sites

2000 ◽  
Vol 68 (1) ◽  
pp. 247-256 ◽  
Author(s):  
Radim Osička ◽  
Adriana Osičková ◽  
Tümay Basar ◽  
Pierre Guermonprez ◽  
Marie Rojas ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Adenylate Cyclase ◽  
Mhc Class I ◽  
Bordetella Pertussis ◽  
Class I ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Presentation Pathway

ABSTRACT Bordetella pertussis adenylate cyclase (AC) toxin-hemolysin (ACT-Hly) can penetrate a variety of eukaryotic cells. Recombinant AC toxoids have therefore been recently used for delivery of CD8+ T-cell epitopes into antigen-presenting cells in vivo and for induction of protective antiviral, as well as therapeutic antitumor cytotoxic T-cell responses. We have explored the carrier potential of the ACT molecule by insertional mutagenesis scanning for new permissive sites, at which integration of two- to nine-residue-long peptides does not interfere with membrane interaction and translocation of ACT. A model CD8+ T-cell epitope of ovalbumin was incorporated at 10 of these permissive sites along the toxin molecule, and the capacity of ACT constructs to penetrate into cell cytosol and deliver the epitope into the major histocompatibility complex (MHC) class I antigen processing and presentation pathway was examined. While all six constructs bearing the epitope within the Hly portion of ACT failed to deliver the epitope to the MHC class I molecules, all four toxoids with inserts within different permissive sites in the AC domain efficiently delivered the epitope into this cytosolic pathway, giving rise to stimulation of a specific CD8+ T-cell hybridoma. The results suggest that, in contrast to the AC domain, the hemolysin moiety of ACT does not reach the cytosolic entry of the MHC class I pathway.

scholarly journals The Length Distribution of Class I–Restricted T Cell Epitopes Is Determined by Both Peptide Supply and MHC Allele–Specific Binding Preference

2016 ◽  
Vol 196 (4) ◽  
pp. 1480-1487 ◽  
Author(s):  
Thomas Trolle ◽  
Curtis P. McMurtrey ◽  
John Sidney ◽  
Wilfried Bardet ◽  
Sean C. Osborn ◽  
...  
Keyword(s):  
T Cell ◽  
Specific Binding ◽  
Length Distribution ◽  
Class I ◽  
T Cell Epitopes ◽  
Binding Preference ◽  
Allele Specific

scholarly journals Different Aspects Concerning Viral Infection and the Role of MHC Molecules in Viral Prevention

2021 ◽  
Vol 15 (1) ◽  
pp. 72-76
Author(s):  
Tirasak Pasharawipas
Keyword(s):  
T Cell ◽  
Viral Infection ◽  
T Lymphocyte ◽  
Cell Clone ◽  
Cell Epitope ◽  
Class I ◽  
T Cell Epitopes ◽  
Mhc Molecules ◽  
T Cell Clone ◽  
Viral Vaccine

Major Histocompatibility Complex (MHC) molecules play a crucial role in inducing an adaptive immune response. T-cell epitopes require compatible MHC molecules to form MHC-peptide Complexes (pMHC) that activate the T-cell Receptors (TCR) of T-lymphocyte clones. MHCs are polymorphic molecules with wide varieties of gene alleles. There are two classes of MHC molecules, class I and II. Both classes have three classical loci HLA-A, -B, and –C are present in class I and HLA-DP, -DQ, and -DR in class II. To induce a compatible T-lymphocyte clone, the T-cell epitope requires the association of the compatible MHC molecule to form pMHC. Each MHC variant possesses a different groove that is capable of binding a different range of antigenic epitopes. Without the compatible MHC molecule, a T cell clone cannot be activated by a particular viral epitope. With the aim of preventing viral transmission, the efficiency of a viral vaccine is related to the existence of specific MHC alleles in the individual. This article proposes the roles of the MHC molecule to prevent viral infection. In addition, the association of the viral receptor molecule with the viral infection will also be discussed.

scholarly journals A theory for how the antigen presentation profile influences the timing of T-cell detection

2018 ◽  
Author(s):  
Alberto Carignano ◽  
Neil Dalchau
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Peptide Binding ◽  
Peptide Sequence ◽  
Class I ◽  
Cell Detection ◽  
Mhc Molecules ◽  
Optimal Degree ◽  
Antigen Presenting

T-cells are activated when their receptor molecules recognize complexes of MHC proteins bound to peptides on the surface of neighbouring cells. Each T-cell expresses one variant of many possible receptor molecules, which are generated through a partially random process that culminates in approximately 107 possible T-cell receptors. As the peptide sequence bound to an MHC molecule is also highly variable, the optimal strategy of an antigen-presenting cell for displaying peptide-MHC complexes is not obvious. A natural compromise arises between aggressive peptide filtering, displaying a few peptides with high stability MHC binding in high abundance and regularity, and promiscuous peptide binding, which can result in more diverse peptides being presented, but in lower abundance. To study this compromise, we have combined a model of MHC class I peptide filtering with a simple probabilistic description of the interactions between antigen presenting cells (APCs) and cytotoxic Tcells (CTLs). By asking how long it takes, on average, for an APC to encounter a circulating CTL that recognises one of the peptides being presented by its MHC molecules, we found that there often exists an optimal degree of peptide filtering, which minimises this expected time until first encounter. The optimal degree of filtering is often in the range of values that the chaperone molecule tapasin confers on peptide selection, but varies between MHC class I molecules that have different peptide binding properties. Our model-based analysis therefore helps to understand how variations in the antigen presentation profile might be exploited for vaccine design or immunotherapies.

Prediction of Prophylactic Peptide Vaccine Candidates for Human Papillomavirus (HPV): An Immunoinformatics and Reverse Vaccinology Approach

2020 ◽  
Vol 17 ◽  
Author(s):  
Mehreen Ismail ◽  
Zureesha Sajid ◽  
Amjad Ali ◽  
Xiaogang Wu ◽  
Syed Aun Muhammad ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
Binding Affinity ◽  
Cd8 T Cells ◽  
Reverse Vaccinology ◽  
Host Immune System ◽  
T Cell Epitopes ◽  
Multiple Alleles ◽  
Vaccine Candidates

Background: Human Papillomavirus (HPV) is responsible for substantial morbidity and mortality worldwide. We predicted immunogenic promiscuous monovalent and polyvalent T-cell epitopes from the polyprotein of the Human Papillomavirus (HPV) using a range of bioinformatics tools and servers. Methods: We used immunoinformatics and reverse vaccinology-based approaches to design prophylactic peptides by antigenicity analysis, Tcell epitopes prediction, proteasomal and conservancy evaluation, host-pathogen protein interactions, and in silico binding affinity analysis. Results: We found two early proteins (E2 and E6) and two late proteins (L1 and L2) of HPV as potential vaccine candidates. Of these proteins (E2, E6, L1 & L2), 2-epitopes of each candidate protein for multiple alleles of MHC class I and II bearing significant binding affinity (>-6.0 kcal/mole). These potential epitopes for CD4+ and CD8+ T-cells were also linked to design polyvalent construct using GPGPG linkers. Cholera toxin B and mycobacterial heparin-binding hemagglutinin adjuvant with a molecular weight of 12.5 and 18.5 kDa were used for epitopes of CD4+ and CD8+ T-cells respectively. The molecular docking indicated the optimum binding affinity of HPV peptides with MHC molecules. This interaction showed that our predicted vaccine candidates are suitable to trigger the host immune system to prevent HPV infections. Conclusion: The predicted conserved T-cell epitopes would contribute to the imminent design of HPV vaccine candidates, which will be able to induce a broad range of immune-responses in a heterogeneous HLA population.

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