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Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response

Vaccines encoding xenoantigens, “non-self” proteins that are highly homologous to their autologous counterparts, have been investigated as a means to increase immunogenicity and overcome tolerance to “self” antigens. We have previously shown that DNA vaccines encoding native prostatic acid phosphata...

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Detalles Bibliográficos
Autores principales: Johnson, Laura E., Frye, Thomas P., McNeel, Douglas G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525610/
https://www.ncbi.nlm.nih.gov/pubmed/23264901
http://dx.doi.org/10.4161/onci.22564
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author Johnson, Laura E.
Frye, Thomas P.
McNeel, Douglas G.
author_facet Johnson, Laura E.
Frye, Thomas P.
McNeel, Douglas G.
author_sort Johnson, Laura E.
collection PubMed
description Vaccines encoding xenoantigens, “non-self” proteins that are highly homologous to their autologous counterparts, have been investigated as a means to increase immunogenicity and overcome tolerance to “self” antigens. We have previously shown that DNA vaccines encoding native prostatic acid phosphatase (PAP) were able to elicit PAP-specific T cells in both rats and humans, but required multiple immunization courses. In this study, we investigated in a preclinical model whether immunizations with a DNA vaccine encoding a xenoantigen could elicit a cross-reactive immune response to the native protein, potentially requiring fewer immunizations. Lewis rats were immunized with a DNA vaccine encoding human PAP and splenocytes from immunized rats were screened with a human peptide library containing overlapping, 15-mer PAP-derived peptides using T-cell proliferation and interferon γ (IFNγ) release as measures of the immune response. One dominant PAP-specific, RT1.A(l)-restricted, epitope was identified. Direct immunization with the immunodominant peptide (HP(201–215)) containing this epitope demonstrated that it included a naturally presented MHC Class I epitope recognized by CD8(+) T cells in Lewis rats. However, no cross-reactive immune response was elicited to the corresponding rat peptide despite a difference of only three amino acids. Immunization with DNA vaccines encoding rat PAP (rPAP) in which this foreign dominant epitope was included as well as with DNA vaccines coding for a variant of the xenoantigen from which this epitope was deleted, did not elicit responses to the native antigen. Overall, these results indicate that the immunization with a xenoantigen-coding DNA vaccine can lead to an immune response which potentially favors foreign epitopes and hence limits any cross-reactive response to the native antigen.
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spelling pubmed-35256102012-12-21 Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response Johnson, Laura E. Frye, Thomas P. McNeel, Douglas G. Oncoimmunology Research Paper Vaccines encoding xenoantigens, “non-self” proteins that are highly homologous to their autologous counterparts, have been investigated as a means to increase immunogenicity and overcome tolerance to “self” antigens. We have previously shown that DNA vaccines encoding native prostatic acid phosphatase (PAP) were able to elicit PAP-specific T cells in both rats and humans, but required multiple immunization courses. In this study, we investigated in a preclinical model whether immunizations with a DNA vaccine encoding a xenoantigen could elicit a cross-reactive immune response to the native protein, potentially requiring fewer immunizations. Lewis rats were immunized with a DNA vaccine encoding human PAP and splenocytes from immunized rats were screened with a human peptide library containing overlapping, 15-mer PAP-derived peptides using T-cell proliferation and interferon γ (IFNγ) release as measures of the immune response. One dominant PAP-specific, RT1.A(l)-restricted, epitope was identified. Direct immunization with the immunodominant peptide (HP(201–215)) containing this epitope demonstrated that it included a naturally presented MHC Class I epitope recognized by CD8(+) T cells in Lewis rats. However, no cross-reactive immune response was elicited to the corresponding rat peptide despite a difference of only three amino acids. Immunization with DNA vaccines encoding rat PAP (rPAP) in which this foreign dominant epitope was included as well as with DNA vaccines coding for a variant of the xenoantigen from which this epitope was deleted, did not elicit responses to the native antigen. Overall, these results indicate that the immunization with a xenoantigen-coding DNA vaccine can lead to an immune response which potentially favors foreign epitopes and hence limits any cross-reactive response to the native antigen. Landes Bioscience 2012-12-01 /pmc/articles/PMC3525610/ /pubmed/23264901 http://dx.doi.org/10.4161/onci.22564 Text en Copyright © 2012 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Research Paper
Johnson, Laura E.
Frye, Thomas P.
McNeel, Douglas G.
Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response
title Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response
title_full Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response
title_fullStr Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response
title_full_unstemmed Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response
title_short Immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific T-cell response
title_sort immunization with a prostate cancer xenoantigen elicits a xenoantigen epitope-specific t-cell response
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525610/
https://www.ncbi.nlm.nih.gov/pubmed/23264901
http://dx.doi.org/10.4161/onci.22564
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