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Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity

In the context of HLA-DP-mismatched allogeneic stem cell transplantation, mismatched HLA-DP alleles can provoke profound allo-HLA-DP-specific immune responses from the donor T-cell repertoire leading to graft-versus-leukemia effect and/or graft-versus-host disease in the patient. The magnitude of al...

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Autores principales: Laghmouchi, Aicha, Kester, Michel G. D., Hoogstraten, Conny, Hageman, Lois, de Klerk, Wendy, Huisman, Wesley, Koster, Eva A. S., de Ru, Arnoud H., van Balen, Peter, Klobuch, Sebastian, van Veelen, Peter A., Falkenburg, J. H. Frederik, Jedema, Inge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888658/
https://www.ncbi.nlm.nih.gov/pubmed/35251023
http://dx.doi.org/10.3389/fimmu.2022.831822
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author Laghmouchi, Aicha
Kester, Michel G. D.
Hoogstraten, Conny
Hageman, Lois
de Klerk, Wendy
Huisman, Wesley
Koster, Eva A. S.
de Ru, Arnoud H.
van Balen, Peter
Klobuch, Sebastian
van Veelen, Peter A.
Falkenburg, J. H. Frederik
Jedema, Inge
author_facet Laghmouchi, Aicha
Kester, Michel G. D.
Hoogstraten, Conny
Hageman, Lois
de Klerk, Wendy
Huisman, Wesley
Koster, Eva A. S.
de Ru, Arnoud H.
van Balen, Peter
Klobuch, Sebastian
van Veelen, Peter A.
Falkenburg, J. H. Frederik
Jedema, Inge
author_sort Laghmouchi, Aicha
collection PubMed
description In the context of HLA-DP-mismatched allogeneic stem cell transplantation, mismatched HLA-DP alleles can provoke profound allo-HLA-DP-specific immune responses from the donor T-cell repertoire leading to graft-versus-leukemia effect and/or graft-versus-host disease in the patient. The magnitude of allo-HLA-DP-specific immune responses has been shown to depend on the specific HLA-DP disparity between donor and patient and the immunogenicity of the mismatched HLA-DP allele(s). HLA-DP peptidome clustering (DPC) was developed to classify the HLA-DP molecules based on similarities and differences in their peptide-binding motifs. To investigate a possible categorization of HLA-DP molecules based on overlap of presented peptides, we identified and compared the peptidomes of the thirteen most frequently expressed HLA-DP molecules. Our categorization based on shared peptides was in line with the DPC classification. We found that the HLA-DP molecules within the previously defined groups DPC-1 or DPC-3 shared the largest numbers of presented peptides. However, the HLA-DP molecules in DPC-2 segregated into two subgroups based on the overlap in presented peptides. Besides overlap in presented peptides within the DPC groups, a substantial number of peptides was also found to be shared between HLA-DP molecules from different DPC groups, especially for groups DPC-1 and -2. The functional relevance of these findings was illustrated by demonstration of cross-reactivity of allo-HLA-DP-reactive T-cell clones not only against HLA-DP molecules within one DPC group, but also across different DPC groups. The promiscuity of peptides presented in various HLA-DP molecules and the cross-reactivity against different HLA-DP molecules demonstrate that these molecules cannot be strictly categorized in immunogenicity groups.
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spelling pubmed-88886582022-03-03 Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity Laghmouchi, Aicha Kester, Michel G. D. Hoogstraten, Conny Hageman, Lois de Klerk, Wendy Huisman, Wesley Koster, Eva A. S. de Ru, Arnoud H. van Balen, Peter Klobuch, Sebastian van Veelen, Peter A. Falkenburg, J. H. Frederik Jedema, Inge Front Immunol Immunology In the context of HLA-DP-mismatched allogeneic stem cell transplantation, mismatched HLA-DP alleles can provoke profound allo-HLA-DP-specific immune responses from the donor T-cell repertoire leading to graft-versus-leukemia effect and/or graft-versus-host disease in the patient. The magnitude of allo-HLA-DP-specific immune responses has been shown to depend on the specific HLA-DP disparity between donor and patient and the immunogenicity of the mismatched HLA-DP allele(s). HLA-DP peptidome clustering (DPC) was developed to classify the HLA-DP molecules based on similarities and differences in their peptide-binding motifs. To investigate a possible categorization of HLA-DP molecules based on overlap of presented peptides, we identified and compared the peptidomes of the thirteen most frequently expressed HLA-DP molecules. Our categorization based on shared peptides was in line with the DPC classification. We found that the HLA-DP molecules within the previously defined groups DPC-1 or DPC-3 shared the largest numbers of presented peptides. However, the HLA-DP molecules in DPC-2 segregated into two subgroups based on the overlap in presented peptides. Besides overlap in presented peptides within the DPC groups, a substantial number of peptides was also found to be shared between HLA-DP molecules from different DPC groups, especially for groups DPC-1 and -2. The functional relevance of these findings was illustrated by demonstration of cross-reactivity of allo-HLA-DP-reactive T-cell clones not only against HLA-DP molecules within one DPC group, but also across different DPC groups. The promiscuity of peptides presented in various HLA-DP molecules and the cross-reactivity against different HLA-DP molecules demonstrate that these molecules cannot be strictly categorized in immunogenicity groups. Frontiers Media S.A. 2022-02-16 /pmc/articles/PMC8888658/ /pubmed/35251023 http://dx.doi.org/10.3389/fimmu.2022.831822 Text en Copyright © 2022 Laghmouchi, Kester, Hoogstraten, Hageman, de Klerk, Huisman, Koster, de Ru, van Balen, Klobuch, van Veelen, Falkenburg and Jedema https://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
Laghmouchi, Aicha
Kester, Michel G. D.
Hoogstraten, Conny
Hageman, Lois
de Klerk, Wendy
Huisman, Wesley
Koster, Eva A. S.
de Ru, Arnoud H.
van Balen, Peter
Klobuch, Sebastian
van Veelen, Peter A.
Falkenburg, J. H. Frederik
Jedema, Inge
Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity
title Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity
title_full Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity
title_fullStr Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity
title_full_unstemmed Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity
title_short Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity
title_sort promiscuity of peptides presented in hla-dp molecules from different immunogenicity groups is associated with t-cell cross-reactivity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888658/
https://www.ncbi.nlm.nih.gov/pubmed/35251023
http://dx.doi.org/10.3389/fimmu.2022.831822
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