How frequently are predicted peptides actually recognized by CD8 cells?

How frequently are predicted peptides actually recognized by CD8 cells?

Detection of antigen-specific CD8 cells frequently relies on the use of peptides that are predicted to bind to HLA Class I molecules or have been shown to induce immune responses. There is extensive knowledge on individual HLA alleles’ peptide-binding requirements, and immunogenic peptides for many...

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Main Authors: Moldovan, Ioana, Targoni, Oleg, Zhang, Wenji, Sundararaman, Srividya, Lehmann, Paul V.
Format: Online
Language:English
Published: Springer Berlin Heidelberg 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917593/
id pubmed-4917593
recordtype oai_dc
spelling pubmed-49175932016-07-07 How frequently are predicted peptides actually recognized by CD8 cells? Moldovan, Ioana Targoni, Oleg Zhang, Wenji Sundararaman, Srividya Lehmann, Paul V. Focussed Research Review Detection of antigen-specific CD8 cells frequently relies on the use of peptides that are predicted to bind to HLA Class I molecules or have been shown to induce immune responses. There is extensive knowledge on individual HLA alleles’ peptide-binding requirements, and immunogenic peptides for many antigens have been defined. The 32 individual peptides that comprise the CEF peptide pool represent such well-defined peptide determinants for Cytomegalo-, Epstein–barr-, and Influenza virus. We tested the accuracy of these peptide recognition predictions on 42 healthy human donors that have been high-resolution HLA-typed. According to the predictions, 241 recall responses should have been detected in these donors. Actual testing showed that 36 (15 %) of the predicted CD8 cell responses occurred in the high frequency range, 41 (17 %) in mid-frequencies, and 45 (19 %) were at the detection limit. In 119 instances (49 %), the predicted peptides were not targeted by CD8 cells detectably. The individual CEF peptides were recognized in an unpredicted fashion in 57 test cases. Moreover, the frequency of CD8 cells responding to a single peptide did not reflect on the number of CD8 cells targeting other determinants on the same antigen. Thus, reliance on one or a few predicted peptides provides a rather inaccurate assessment of antigen-specific CD8 cell immunity, strongly arguing for the use of peptide pools for immune monitoring. Springer Berlin Heidelberg 2016-04-23 2016 /pmc/articles/PMC4917593/ /pubmed/27108305 http://dx.doi.org/10.1007/s00262-016-1840-7 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Moldovan, Ioana
Targoni, Oleg
Zhang, Wenji
Sundararaman, Srividya
Lehmann, Paul V.
spellingShingle Moldovan, Ioana
Targoni, Oleg
Zhang, Wenji
Sundararaman, Srividya
Lehmann, Paul V.
How frequently are predicted peptides actually recognized by CD8 cells?
author_facet Moldovan, Ioana
Targoni, Oleg
Zhang, Wenji
Sundararaman, Srividya
Lehmann, Paul V.
author_sort Moldovan, Ioana
title How frequently are predicted peptides actually recognized by CD8 cells?
title_short How frequently are predicted peptides actually recognized by CD8 cells?
title_full How frequently are predicted peptides actually recognized by CD8 cells?
title_fullStr How frequently are predicted peptides actually recognized by CD8 cells?
title_full_unstemmed How frequently are predicted peptides actually recognized by CD8 cells?
title_sort how frequently are predicted peptides actually recognized by cd8 cells?
description Detection of antigen-specific CD8 cells frequently relies on the use of peptides that are predicted to bind to HLA Class I molecules or have been shown to induce immune responses. There is extensive knowledge on individual HLA alleles’ peptide-binding requirements, and immunogenic peptides for many antigens have been defined. The 32 individual peptides that comprise the CEF peptide pool represent such well-defined peptide determinants for Cytomegalo-, Epstein–barr-, and Influenza virus. We tested the accuracy of these peptide recognition predictions on 42 healthy human donors that have been high-resolution HLA-typed. According to the predictions, 241 recall responses should have been detected in these donors. Actual testing showed that 36 (15 %) of the predicted CD8 cell responses occurred in the high frequency range, 41 (17 %) in mid-frequencies, and 45 (19 %) were at the detection limit. In 119 instances (49 %), the predicted peptides were not targeted by CD8 cells detectably. The individual CEF peptides were recognized in an unpredicted fashion in 57 test cases. Moreover, the frequency of CD8 cells responding to a single peptide did not reflect on the number of CD8 cells targeting other determinants on the same antigen. Thus, reliance on one or a few predicted peptides provides a rather inaccurate assessment of antigen-specific CD8 cell immunity, strongly arguing for the use of peptide pools for immune monitoring.
publisher Springer Berlin Heidelberg
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917593/
_version_ 1613598360343674880

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