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T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells

These studies tested whether antigenic competition between T cells occurs. We generated CD8(+) T cell responses in H-2(b) mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendriti...

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Autores principales: Kedl, Ross M., Rees, William A., Hildeman, David A., Schaefer, Brian, Mitchell, Tom, Kappler, John, Marrack, Philippa
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195874/
https://www.ncbi.nlm.nih.gov/pubmed/11034600
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author Kedl, Ross M.
Rees, William A.
Hildeman, David A.
Schaefer, Brian
Mitchell, Tom
Kappler, John
Marrack, Philippa
author_facet Kedl, Ross M.
Rees, William A.
Hildeman, David A.
Schaefer, Brian
Mitchell, Tom
Kappler, John
Marrack, Philippa
author_sort Kedl, Ross M.
collection PubMed
description These studies tested whether antigenic competition between T cells occurs. We generated CD8(+) T cell responses in H-2(b) mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8(+) T cell responses were visualized by major histocompatibility complex class I–peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8(+) T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.
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spelling pubmed-21958742008-04-16 T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells Kedl, Ross M. Rees, William A. Hildeman, David A. Schaefer, Brian Mitchell, Tom Kappler, John Marrack, Philippa J Exp Med Original Article These studies tested whether antigenic competition between T cells occurs. We generated CD8(+) T cell responses in H-2(b) mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8(+) T cell responses were visualized by major histocompatibility complex class I–peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8(+) T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets. The Rockefeller University Press 2000-10-16 /pmc/articles/PMC2195874/ /pubmed/11034600 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Kedl, Ross M.
Rees, William A.
Hildeman, David A.
Schaefer, Brian
Mitchell, Tom
Kappler, John
Marrack, Philippa
T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells
title T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells
title_full T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells
title_fullStr T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells
title_full_unstemmed T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells
title_short T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells
title_sort t cells compete for access to antigen-bearing antigen-presenting cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195874/
https://www.ncbi.nlm.nih.gov/pubmed/11034600
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