An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes

We show that cytotoxic T lymphocytes (CTLs) infiltrating a kidney tumor recognize a peptide encoded by an alternative open reading frame (ORF) of the macrophage colony-stimulating factor (M-CSF) gene. Remarkably, this alternative ORF, which is translated in many tumors concurrently with the major OR...

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Main Authors: Probst-Kepper, Michael, Stroobant, Vincent, Kridel, Robert, Gaugler, Béatrice, Landry, Claire, Brasseur, Francis, Cosyns, Jean-Pierre, Weynand, Birgit, Boon, Thierry, Van den Eynde, Benoit J.
Format: Online
Language:English
Published: The Rockefeller University Press 2001
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193327/
id pubmed-2193327
recordtype oai_dc
spelling pubmed-21933272008-04-14 An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes Probst-Kepper, Michael Stroobant, Vincent Kridel, Robert Gaugler, Béatrice Landry, Claire Brasseur, Francis Cosyns, Jean-Pierre Weynand, Birgit Boon, Thierry Van den Eynde, Benoit J. Original Article We show that cytotoxic T lymphocytes (CTLs) infiltrating a kidney tumor recognize a peptide encoded by an alternative open reading frame (ORF) of the macrophage colony-stimulating factor (M-CSF) gene. Remarkably, this alternative ORF, which is translated in many tumors concurrently with the major ORF, is also translated in some tissues that do not produce M-CSF, such as liver and kidney. Such a dissociation of the translation of two overlapping ORFs from the same gene is unexpected. The antigenic peptide encoded by the alternative ORF is presented by human histocompatibility leukocyte antigen (HLA)-B*3501 and has a length of 14 residues. Peptide elution indicated that tumor cells naturally present this 14 mer, which is the longest peptide known to be recognized by CTLs. Binding studies of peptide analogues suggest that it binds by its two extremities and bulges out of the HLA groove to compensate for its length. The Rockefeller University Press 2001-05-21 /pmc/articles/PMC2193327/ /pubmed/11369790 Text en © 2001 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/).
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 Probst-Kepper, Michael
Stroobant, Vincent
Kridel, Robert
Gaugler, Béatrice
Landry, Claire
Brasseur, Francis
Cosyns, Jean-Pierre
Weynand, Birgit
Boon, Thierry
Van den Eynde, Benoit J.
spellingShingle Probst-Kepper, Michael
Stroobant, Vincent
Kridel, Robert
Gaugler, Béatrice
Landry, Claire
Brasseur, Francis
Cosyns, Jean-Pierre
Weynand, Birgit
Boon, Thierry
Van den Eynde, Benoit J.
An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes
author_facet Probst-Kepper, Michael
Stroobant, Vincent
Kridel, Robert
Gaugler, Béatrice
Landry, Claire
Brasseur, Francis
Cosyns, Jean-Pierre
Weynand, Birgit
Boon, Thierry
Van den Eynde, Benoit J.
author_sort Probst-Kepper, Michael
title An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes
title_short An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes
title_full An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes
title_fullStr An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes
title_full_unstemmed An Alternative Open Reading Frame of the Human Macrophage Colony-Stimulating Factor Gene Is Independently Translated and Codes for an Antigenic Peptide of 14 Amino Acids Recognized by Tumor-Infiltrating Cd8 T Lymphocytes
title_sort alternative open reading frame of the human macrophage colony-stimulating factor gene is independently translated and codes for an antigenic peptide of 14 amino acids recognized by tumor-infiltrating cd8 t lymphocytes
description We show that cytotoxic T lymphocytes (CTLs) infiltrating a kidney tumor recognize a peptide encoded by an alternative open reading frame (ORF) of the macrophage colony-stimulating factor (M-CSF) gene. Remarkably, this alternative ORF, which is translated in many tumors concurrently with the major ORF, is also translated in some tissues that do not produce M-CSF, such as liver and kidney. Such a dissociation of the translation of two overlapping ORFs from the same gene is unexpected. The antigenic peptide encoded by the alternative ORF is presented by human histocompatibility leukocyte antigen (HLA)-B*3501 and has a length of 14 residues. Peptide elution indicated that tumor cells naturally present this 14 mer, which is the longest peptide known to be recognized by CTLs. Binding studies of peptide analogues suggest that it binds by its two extremities and bulges out of the HLA groove to compensate for its length.
publisher The Rockefeller University Press
publishDate 2001
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193327/
_version_ 1611431026167382016