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Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells

Antigen presentation by major histocompatibility complex (MHC) class I molecules requires peptide supply by the transporters associated with antigen processing (TAPs), which select substrates in a species- and, in the rat, allele-specific manner. Conflicts between TAPs and MHC preferences for COOH-t...

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Autores principales: Lauvau, Grégoire, Kakimi, Kazuhiro, Niedermann, Gabriele, Ostankovitch, Marina, Yotnda, Patricia, Firat, Hüseyin, Chisari, Francis V., van Endert, Peter M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195672/
https://www.ncbi.nlm.nih.gov/pubmed/10544195
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author Lauvau, Grégoire
Kakimi, Kazuhiro
Niedermann, Gabriele
Ostankovitch, Marina
Yotnda, Patricia
Firat, Hüseyin
Chisari, Francis V.
van Endert, Peter M.
author_facet Lauvau, Grégoire
Kakimi, Kazuhiro
Niedermann, Gabriele
Ostankovitch, Marina
Yotnda, Patricia
Firat, Hüseyin
Chisari, Francis V.
van Endert, Peter M.
author_sort Lauvau, Grégoire
collection PubMed
description Antigen presentation by major histocompatibility complex (MHC) class I molecules requires peptide supply by the transporters associated with antigen processing (TAPs), which select substrates in a species- and, in the rat, allele-specific manner. Conflicts between TAPs and MHC preferences for COOH-terminal peptide residues in rodent cells strongly reduce the efficiency of MHC class I antigen presentation. Although human TAP is relatively permissive, some peptide ligands for human histocompatibility leukocyte antigen class I molecules are known to possess very low TAP affinities; the significance of these in vitro findings for cellular antigen presentation is not known. We studied two naturally immunodominant viral epitopes presented by HLA-A2 that display very low affinities for human TAP. Low TAP affinities preclude minimal epitope access to the endoplasmic reticulum (ER) and assembly with HLA-A2 in vitro, as well as presentation by minigene-expressing cells to cytotoxic T lymphocytes. However, NH(2)-terminally but not COOH-terminally extended epitope variants with higher TAP affinities assemble in vitro and are presented to cytotoxic T lymphocytes with high efficiency. Thus, human TAP can influence epitope selection and restrict access to the ER to epitope precursors. Analysis of TAP affinities of a panel of viral epitopes suggests that TAP selection of precursors may be a common phenomenon for HLA-A2–presented epitopes. We also analyzed HLA-A2–eluted peptides from minigene-expressing cells and show that an NH(2)-terminally extended variant with low A2 binding affinity undergoes ER processing, whereas another with high affinity is presented unmodified. Therefore, the previously reported aminopeptidase activity in the ER can also act on TAP-translocated peptides.
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spelling pubmed-21956722008-04-16 Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells Lauvau, Grégoire Kakimi, Kazuhiro Niedermann, Gabriele Ostankovitch, Marina Yotnda, Patricia Firat, Hüseyin Chisari, Francis V. van Endert, Peter M. J Exp Med Original Article Antigen presentation by major histocompatibility complex (MHC) class I molecules requires peptide supply by the transporters associated with antigen processing (TAPs), which select substrates in a species- and, in the rat, allele-specific manner. Conflicts between TAPs and MHC preferences for COOH-terminal peptide residues in rodent cells strongly reduce the efficiency of MHC class I antigen presentation. Although human TAP is relatively permissive, some peptide ligands for human histocompatibility leukocyte antigen class I molecules are known to possess very low TAP affinities; the significance of these in vitro findings for cellular antigen presentation is not known. We studied two naturally immunodominant viral epitopes presented by HLA-A2 that display very low affinities for human TAP. Low TAP affinities preclude minimal epitope access to the endoplasmic reticulum (ER) and assembly with HLA-A2 in vitro, as well as presentation by minigene-expressing cells to cytotoxic T lymphocytes. However, NH(2)-terminally but not COOH-terminally extended epitope variants with higher TAP affinities assemble in vitro and are presented to cytotoxic T lymphocytes with high efficiency. Thus, human TAP can influence epitope selection and restrict access to the ER to epitope precursors. Analysis of TAP affinities of a panel of viral epitopes suggests that TAP selection of precursors may be a common phenomenon for HLA-A2–presented epitopes. We also analyzed HLA-A2–eluted peptides from minigene-expressing cells and show that an NH(2)-terminally extended variant with low A2 binding affinity undergoes ER processing, whereas another with high affinity is presented unmodified. Therefore, the previously reported aminopeptidase activity in the ER can also act on TAP-translocated peptides. The Rockefeller University Press 1999-11-01 /pmc/articles/PMC2195672/ /pubmed/10544195 Text en © 1999 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
Lauvau, Grégoire
Kakimi, Kazuhiro
Niedermann, Gabriele
Ostankovitch, Marina
Yotnda, Patricia
Firat, Hüseyin
Chisari, Francis V.
van Endert, Peter M.
Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells
title Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells
title_full Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells
title_fullStr Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells
title_full_unstemmed Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells
title_short Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells
title_sort human transporters associated with antigen processing (taps) select epitope precursor peptides for processing in the endoplasmic reticulum and presentation to t cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195672/
https://www.ncbi.nlm.nih.gov/pubmed/10544195
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