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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-8888658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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