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Hierarchy, Tolerance, and Dominance in the Antitumor T-Cell Response

Nicholas P. Restifo
2001 Journal of immunotherapy  
Predicting immunodominant peptides that can be targets for recognition by T cells, also known as allele-specific epitope forecasting, can be done in a variety of ways, but one of the best predictors is  ...  the use of computer programs that predict the ability of peptides to form stable complexes with T cells.  ...  Predicting immunodominant peptides that can be targets for recognition by T cells, also known as allele-specific epitope forecasting, can be done in a variety of ways, but one of the best predictors is  ... 
doi:10.1097/00002371-200105000-00001 pmid:11394495 pmcid:PMC2562287 fatcat:wyqz2fhajrf6bjcrvayqow4ksq

Prediction of Cellular Immune Responses against CFTR in Patients with Cystic Fibrosis after Gene Therapy

Joanita Figueredo, Maria P. Limberis, James M. Wilson
2007 American Journal of Respiratory Cell and Molecular Biology  
However, T cells directed against epitopes that span sequences containing class II-V mutations are also possible.  ...  We used MHC-binding prediction programs to predict the probability of cellular immune responses that may be generated against CFTR in ⌬F508 homozygote patients.  ...  SYFPEITHI is an updated database with previous publications on T cell epitopes and MHC ligands (13) (access via: www.syfpeithi.de) The prediction is based on published motifs (pool sequencing, natural  ... 
doi:10.1165/rcmb.2006-0313cb pmid:17218617 pmcid:PMC1899331 fatcat:fkuyheswevbr5ghk7z5d3iqwri

Alloreactive cytotoxic T cells provide means to decipher the immunopeptidome and reveal a plethora of tumor-associated self-epitopes

S. Kumari, S. Walchli, L.-E. Fallang, W. Yang, F. Lund-Johansen, T. N. Schumacher, J. Olweus
2013 Proceedings of the National Academy of Sciences of the United States of America  
Thus, the utility of T cells for detection of self-peptides presented on self-HLA is limited by tolerance.  ...  HLA molecules presenting peptides derived from tumor-associated self-antigens (self-TAA) are attractive targets for T-cell-based immunotherapy of cancer.  ...  Lind for providing cell lines, to N. A. C. Westerdaal, K. S. Landsverk, and I. Dale Rein for cell sorting, and to the families of Ø. A. Grøseth, R. Stokke, B. Moen Stjern, and E.  ... 
doi:10.1073/pnas.1306549111 pmid:24344295 pmcid:PMC3890872 fatcat:xn7fbzphjjemtgcfuig6y7re5q

It's the Peptide-MHC Affinity, Stupid

Thomas Kammertoens, Thomas Blankenstein
2013 Cancer Cell  
Conversely, cancer vaccines targeting self-TA face the difficulty of not only relying on T cells, which survived central tolerance, but also targeting epitopes of low pMHC affinity.  ...  Peptides predicted with high affinity have rarely been described as T cell epitopes.  ...  On the one hand, this might be related to our still limited ability  ... 
doi:10.1016/j.ccr.2013.04.004 pmid:23597560 fatcat:np5or2f7nvb45iioo3pgr5pmlu

Proteasome-Generated cis-Spliced Peptides and Their Potential Role in CD8+ T Cell Tolerance

Artem Mansurkhodzhaev, Camila R. R. Barbosa, Michele Mishto, Juliane Liepe
2021 Frontiers in Immunology  
The human immune system relies on the capability of CD8+ T cells to patrol body cells, spot infected cells and eliminate them.  ...  Theoretically, they also have a very large sequence variability, which might impinge upon our model of self/non-self discrimination and central and peripheral CD8+ T cell tolerance.  ...  a role in CD8 + T cell tolerance.  ... 
doi:10.3389/fimmu.2021.614276 pmid:33717099 pmcid:PMC7943738 fatcat:zg5jsfer45amrixg3vkyv7p6su

Predicting immunogenicity by modeling the central tolerance of CD8+ T cells in individual patients [article]

Ngoc Hieu Tran, Ming Li
2022 bioRxiv   pre-print
tolerance of T cells.  ...  In particular, for each individual patient, we collected his/her HLA-I self peptides derived from mass spectrometry-based immunopeptidomics as negative selection, and allele-matched immunogenic T cell  ...  Qiao for discussions on the relevant topics.  ... 
doi:10.1101/2022.07.05.497667 fatcat:45t5ilewjzeorgqo3vxxypl6ei

How diverse should the immune system be?

Rob J De Boer, Alan. S. Perelson
1993 Proceedings of the Royal Society of London. Biological Sciences  
Taking into account the fraction of the repertoire that is expected to be rendered tolerant because of potential self reactivity, we calculate PE, the probability that a pathogen escapes recognition by  ...  We develop a probability based model that suggests a novel explanation for the enormous diversity of the lymphocyte repertoire in the immune system.  ...  Ton Logtenberg for helpful comments on earlier versions of the manuscript. This work was performed under the auspices of the U.S. Department of Energy.  ... 
doi:10.1098/rspb.1993.0062 pmid:8394577 fatcat:l5p2tq4vgbafld2fawymahuwj4

Prioritizing putatively etiological T cell epitopes across autoimmune diseases [article]

Masato Ogishi
2019 bioRxiv   pre-print
The HLA class I and class II molecules present epitopes to T cells, and T cells play indispensable roles both in the maintenance of tolerance and the pathogenesis of autoimmune diseases.  ...  Self-epitopes were generally more stably presented on disease-protective HLAs than non-self epitopes, and hence had a negative DPI.  ...  roles of T cells as the master regulator of adaptive immunity and self-tolerance, 76 the contribution of T cell epitope to autoimmune diseases has been extensively studied, and 77 numerous self-and  ... 
doi:10.1101/580126 fatcat:nj64n62x3jal5nciiq2dh5ncke

Novel insights into the HLA class I immunopeptidome and T-cell immunosurveillance

Cornelis J. M. Melief, Jan H. Kessler
2017 Genome Medicine  
These findings have far-reaching implications for immunosurveillance by T cells and translational value for immunotherapy.  ...  Advances in mass spectrometry have allowed the high-throughput quantitative identification of human leukocyte antigen (HLA) class I ligands, and recent studies have reported on the breadth and diversity  ...  Furthermore, the identification of self class I immunopeptidomes and their prediction based on source features enables deprioritization of any predicted vaccine CTL epitope in which the TCR-binding residues  ... 
doi:10.1186/s13073-017-0439-8 pmid:28539110 pmcid:PMC5442872 fatcat:gygssclnofeptnp53gv4csk5ym

Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools

Anne S. De Groot, Leonard Moise, Frances Terry, Andres H. Gutierrez, Pooja Hindocha, Guilhem Richard, Daniel Fredric Hoft, Ted M. Ross, Amy R. Noe, Yoshimasa Takahashi, Vinayaka Kotraiah, Sarah E. Silk (+6 others)
2020 Frontiers in Immunology  
Commercial and academic applications of iVAX have included identifying immunogenic T cell epitopes in the development of a T-cell based human multi-epitope Q fever vaccine, designing novel influenza vaccines  ...  T cell epitopes, and re-designing antigens to induce immunogenicity and protection against disease for humans and livestock.  ...  This may enable a pathogen to trigger "ignorance" or active tolerance from T cells that have been trained on self-epitopes. Adapted from Moise et al.  ... 
doi:10.3389/fimmu.2020.00442 pmid:32318055 pmcid:PMC7154102 fatcat:54x6hl32dbay3ps47op6yddzze

Tolerogenic vaccines for Multiple Sclerosis

Mark D. Mannie, Alan D. Curtis, II
2013 Human Vaccines & Immunotherapeutics  
Because tolerogenic vaccines contain native myelin epitopes, tolerogenic vaccination would predictably reinforce regulatory T cell function and the low efficiency interactions that promote tolerance rather  ...  On the opposite side of the spectrum, MS vaccines may need to be individualized vaccines that cover numerous and highly diverse myelin epitopes based on unique sets of reactivities for each patient.  ... 
doi:10.4161/hv.23685 pmid:23357858 pmcid:PMC3899137 fatcat:orsrkzwzlfdf3fsmzlb5frqy4u

Can we prevent immunogenicity of human protein drugs?

D W Scott, A S De Groot
2009 Annals of the Rheumatic Diseases  
In principle, humanised and fully human monoclonal antibodies are "self" immunoglobulins and should be tolerated.  ...  Finally, novel approaches to "re-induce" immunological tolerance to these proteins, including gene therapy and the recognition of unique regulatory epitopes, are outlined.  ...  Based on the number of such HLA-binding epitopes per unit (total number of epitopes divided by the total number of amino acids) one might successfully predict that certain monoclonal antibodies or protein  ... 
doi:10.1136/ard.2009.117564 pmid:19995750 fatcat:4etbaqtxb5d3hlbkv5aj45jfqu

T cell epitope: Friend or Foe? Immunogenicity of biologics in context☆

Constanze A. Weber, Preema J. Mehta, Matt Ardito, Lenny Moise, Bill Martin, Anne S. De Groot
2009 Advanced Drug Delivery Reviews  
T cell epitopes are at the root of the immunogenicity issue. Through their presentation to T cells, they activate the process of anti-drug antibody development.  ...  Preclinical screening for T cell epitopes can be performed in silico, followed by in vitro and in vivo validation.  ...  The concept of epitope density emerged from discussions with Gene Koren and Paul Knopf, whose contributions to the immunogenicity scale are hereby gratefully acknowledged.  ... 
doi:10.1016/j.addr.2009.07.001 pmid:19619593 pmcid:PMC7103283 fatcat:d2sdcgusvjb2feuyyl2m45gbs4

Prediction of immunogenicity for therapeutic proteins: state of the art

Anne S De Groot, Leonard Moise
2007 Current opinion in drug discovery & development  
of regulatory T-cells.  ...  protein that, when processed by T-cells, elicit an immune response.  ...  Selecting peptides for immunogenicity assays based on epitope prediction tools is an alternative approach.  ... 
pmid:17554860 fatcat:tpxrwfonlzcvfnouos4wnafgqy

Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics

Anne S De Groot, Frances Terry, Leslie Cousens, William Martin
2013 Expert Review of Clinical Pharmacology  
the self-reactive T cells.  ...  For T cells, self/non-self discrimination initially occurs in the thymus during T-cell maturation when medullary epithelial cells present tissue-specific self-protein epitopes, in the context of MHC, to  ... 
doi:10.1586/17512433.2013.835698 pmid:24164613 pmcid:PMC4086238 fatcat:zppv7c7lgrdvhm676jzw2mwmve
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