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Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens
Patients undergoing allogeneic stem cell transplantation as treatment for hematological diseases face the risk of Graft-versus-Host Disease as well as relapse. Graft-versus-Host Disease and the favorable Graft-versus-Leukemia effect are mediated by donor T cells recognizing polymorphic peptides, whi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180171/ https://www.ncbi.nlm.nih.gov/pubmed/32362897 http://dx.doi.org/10.3389/fimmu.2020.00659 |
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author | Fuchs, Kyra J. Honders, M. Willy van der Meijden, Edith D. Adriaans, Alwin E. van der Lee, Dyantha I. Pont, Margot J. Monajemi, Ramin Kielbasa, Szymon M. ’t Hoen, Peter A. C. van Bergen, Cornelis A. M. Falkenburg, J. H. Frederik Griffioen, Marieke |
author_facet | Fuchs, Kyra J. Honders, M. Willy van der Meijden, Edith D. Adriaans, Alwin E. van der Lee, Dyantha I. Pont, Margot J. Monajemi, Ramin Kielbasa, Szymon M. ’t Hoen, Peter A. C. van Bergen, Cornelis A. M. Falkenburg, J. H. Frederik Griffioen, Marieke |
author_sort | Fuchs, Kyra J. |
collection | PubMed |
description | Patients undergoing allogeneic stem cell transplantation as treatment for hematological diseases face the risk of Graft-versus-Host Disease as well as relapse. Graft-versus-Host Disease and the favorable Graft-versus-Leukemia effect are mediated by donor T cells recognizing polymorphic peptides, which are presented on the cell surface by HLA molecules and result from single nucleotide polymorphism alleles that are disparate between patient and donor. Identification of polymorphic HLA-binding peptides, designated minor histocompatibility antigens, has been a laborious procedure, and the number and scope for broad clinical use of these antigens therefore remain limited. Here, we present an optimized whole genome association approach for discovery of HLA class I minor histocompatibility antigens. T cell clones isolated from patients who responded to donor lymphocyte infusions after HLA-matched allogeneic stem cell transplantation were tested against a panel of 191 EBV-transformed B cells, which have been sequenced by the 1000 Genomes Project and selected for expression of seven common HLA class I alleles (HLA-A(∗)01:01, A(∗)02:01, A(∗)03:01, B(∗)07:02, B(∗)08:01, C(∗)07:01, and C(∗)07:02). By including all polymorphisms with minor allele frequencies above 0.01, we demonstrated that the new approach allows direct discovery of minor histocompatibility antigens as exemplified by seven new antigens in eight different HLA class I alleles including one antigen in HLA-A(∗)24:02 and HLA-A(∗)23:01, for which the method has not been originally designed. Our new whole genome association strategy is expected to rapidly augment the repertoire of HLA class I-restricted minor histocompatibility antigens that will become available for donor selection and clinical use to predict, follow or manipulate Graft-versus-Leukemia effect and Graft-versus-Host Disease after allogeneic stem cell transplantation. |
format | Online Article Text |
id | pubmed-7180171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71801712020-05-01 Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens Fuchs, Kyra J. Honders, M. Willy van der Meijden, Edith D. Adriaans, Alwin E. van der Lee, Dyantha I. Pont, Margot J. Monajemi, Ramin Kielbasa, Szymon M. ’t Hoen, Peter A. C. van Bergen, Cornelis A. M. Falkenburg, J. H. Frederik Griffioen, Marieke Front Immunol Immunology Patients undergoing allogeneic stem cell transplantation as treatment for hematological diseases face the risk of Graft-versus-Host Disease as well as relapse. Graft-versus-Host Disease and the favorable Graft-versus-Leukemia effect are mediated by donor T cells recognizing polymorphic peptides, which are presented on the cell surface by HLA molecules and result from single nucleotide polymorphism alleles that are disparate between patient and donor. Identification of polymorphic HLA-binding peptides, designated minor histocompatibility antigens, has been a laborious procedure, and the number and scope for broad clinical use of these antigens therefore remain limited. Here, we present an optimized whole genome association approach for discovery of HLA class I minor histocompatibility antigens. T cell clones isolated from patients who responded to donor lymphocyte infusions after HLA-matched allogeneic stem cell transplantation were tested against a panel of 191 EBV-transformed B cells, which have been sequenced by the 1000 Genomes Project and selected for expression of seven common HLA class I alleles (HLA-A(∗)01:01, A(∗)02:01, A(∗)03:01, B(∗)07:02, B(∗)08:01, C(∗)07:01, and C(∗)07:02). By including all polymorphisms with minor allele frequencies above 0.01, we demonstrated that the new approach allows direct discovery of minor histocompatibility antigens as exemplified by seven new antigens in eight different HLA class I alleles including one antigen in HLA-A(∗)24:02 and HLA-A(∗)23:01, for which the method has not been originally designed. Our new whole genome association strategy is expected to rapidly augment the repertoire of HLA class I-restricted minor histocompatibility antigens that will become available for donor selection and clinical use to predict, follow or manipulate Graft-versus-Leukemia effect and Graft-versus-Host Disease after allogeneic stem cell transplantation. Frontiers Media S.A. 2020-04-17 /pmc/articles/PMC7180171/ /pubmed/32362897 http://dx.doi.org/10.3389/fimmu.2020.00659 Text en Copyright © 2020 Fuchs, Honders, van der Meijden, Adriaans, van der Lee, Pont, Monajemi, Kielbasa, ’t Hoen, van Bergen, Falkenburg and Griffioen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Fuchs, Kyra J. Honders, M. Willy van der Meijden, Edith D. Adriaans, Alwin E. van der Lee, Dyantha I. Pont, Margot J. Monajemi, Ramin Kielbasa, Szymon M. ’t Hoen, Peter A. C. van Bergen, Cornelis A. M. Falkenburg, J. H. Frederik Griffioen, Marieke Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens |
title | Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens |
title_full | Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens |
title_fullStr | Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens |
title_full_unstemmed | Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens |
title_short | Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens |
title_sort | optimized whole genome association scanning for discovery of hla class i-restricted minor histocompatibility antigens |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180171/ https://www.ncbi.nlm.nih.gov/pubmed/32362897 http://dx.doi.org/10.3389/fimmu.2020.00659 |
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