A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

Minor histocompatibility antigens (minor H antigens) are targets of graft-versus-host disease and graft-versus-leukemia responses after allogeneic human leukocyte antigen identical hematopoietic stem cell transplantation. Only a few human minor H antigens have been molecularly characterized and in a...

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Main Authors: Murata, Makoto, Warren, Edus H., Riddell, Stanley R.
Format: Online
Language:English
Published: The Rockefeller University Press 2003
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193779/
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recordtype oai_dc
spelling pubmed-21937792008-04-11 A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion Murata, Makoto Warren, Edus H. Riddell, Stanley R. Article Minor histocompatibility antigens (minor H antigens) are targets of graft-versus-host disease and graft-versus-leukemia responses after allogeneic human leukocyte antigen identical hematopoietic stem cell transplantation. Only a few human minor H antigens have been molecularly characterized and in all cases, amino acid differences between homologous donor and recipient proteins due to nucleotide polymorphisms in the respective genes were responsible for immunogenicity. Here, we have used cDNA expression cloning to identify a novel human minor H antigen encoded by UGT2B17, an autosomal gene in the multigene UDP-glycosyltransferase 2 family that is selectively expressed in liver, intestine, and antigen-presenting cells. In contrast to previously defined human minor H antigens, UGT2B17 is immunogenic because of differential expression of the protein in donor and recipient cells as a consequence of a homozygous gene deletion in the donor. Deletion of individual members of large gene families is a common form of genetic variation in the population and our results provide the first evidence that differential protein expression as a consequence of gene deletion is a mechanism for generating minor H antigens in humans. The Rockefeller University Press 2003-05-19 /pmc/articles/PMC2193779/ /pubmed/12743171 http://dx.doi.org/10.1084/jem.20030044 Text en Copyright © 2003, 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 Murata, Makoto
Warren, Edus H.
Riddell, Stanley R.
spellingShingle Murata, Makoto
Warren, Edus H.
Riddell, Stanley R.
A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion
author_facet Murata, Makoto
Warren, Edus H.
Riddell, Stanley R.
author_sort Murata, Makoto
title A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion
title_short A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion
title_full A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion
title_fullStr A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion
title_full_unstemmed A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion
title_sort human minor histocompatibility antigen resulting from differential expression due to a gene deletion
description Minor histocompatibility antigens (minor H antigens) are targets of graft-versus-host disease and graft-versus-leukemia responses after allogeneic human leukocyte antigen identical hematopoietic stem cell transplantation. Only a few human minor H antigens have been molecularly characterized and in all cases, amino acid differences between homologous donor and recipient proteins due to nucleotide polymorphisms in the respective genes were responsible for immunogenicity. Here, we have used cDNA expression cloning to identify a novel human minor H antigen encoded by UGT2B17, an autosomal gene in the multigene UDP-glycosyltransferase 2 family that is selectively expressed in liver, intestine, and antigen-presenting cells. In contrast to previously defined human minor H antigens, UGT2B17 is immunogenic because of differential expression of the protein in donor and recipient cells as a consequence of a homozygous gene deletion in the donor. Deletion of individual members of large gene families is a common form of genetic variation in the population and our results provide the first evidence that differential protein expression as a consequence of gene deletion is a mechanism for generating minor H antigens in humans.
publisher The Rockefeller University Press
publishDate 2003
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193779/
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