Sampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificity
Comprehensive analysis of the complex nature of the Human Leukocyte Antigen (HLA) class II ligandome is of utmost importance to understand the basis for CD4+ T cell mediated immunity and tolerance. Here, we implemented important improvements in the analysis of the repertoire of HLA-DR-presented pept...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Published: |
American Society for Biochemistry and Molecular Biology
2016
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| _version_ | 1797075173710495744 |
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| author | Mommen, G Marino, F Meiring, H Poelen, M van Gaans-van den Brink, J Mohammed, S Heck, A van Els, C |
| author_facet | Mommen, G Marino, F Meiring, H Poelen, M van Gaans-van den Brink, J Mohammed, S Heck, A van Els, C |
| author_sort | Mommen, G |
| collection | OXFORD |
| description | Comprehensive analysis of the complex nature of the Human Leukocyte Antigen (HLA) class II ligandome is of utmost importance to understand the basis for CD4+ T cell mediated immunity and tolerance. Here, we implemented important improvements in the analysis of the repertoire of HLA-DR-presented peptides, using hybrid mass spectrometry-based peptide fragmentation techniques on a ligandome sample isolated from matured human monocyte-derived dendritic cells (DC). The reported data set constitutes nearly 14 thousand unique high-confident peptides, i.e. the largest single inventory of human DC derived HLA-DR ligands to date. From a technical viewpoint the most prominent finding is that no single peptide fragmentation technique could elucidate the majority of HLA-DR ligands, because of the wide range of physical chemical properties displayed by the HLA-DR ligandome. Our in-depth profiling allowed us to reveal a strikingly poor correlation between the source proteins identified in the HLA class II ligandome and the DC cellular proteome. Important selective sieving from the sampled proteome to the ligandome was evidenced by specificity in the sequences of the core regions both at their N- and C- termini, hence not only reflecting binding motifs but also dominant protease activity associated to the endolysosomal compartments. Moreover, we demonstrate that the HLA-DR ligandome reflects a surface representation of cell-compartments specific for biological events linked to the maturation of monocytes into antigen presenting cells. Our results present new perspectives into the complex nature of the HLA class II system and will aid future immunological studies in characterizing the full breadth of potential CD4+ T cell epitopes relevant in health and disease. |
| first_indexed | 2024-03-06T23:46:37Z |
| format | Journal article |
| id | oxford-uuid:71234e52-43db-42fe-918e-983b6b905896 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:46:37Z |
| publishDate | 2016 |
| publisher | American Society for Biochemistry and Molecular Biology |
| record_format | dspace |
| spelling | oxford-uuid:71234e52-43db-42fe-918e-983b6b9058962022-03-26T19:41:39ZSampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:71234e52-43db-42fe-918e-983b6b905896Symplectic Elements at OxfordAmerican Society for Biochemistry and Molecular Biology2016Mommen, GMarino, FMeiring, HPoelen, Mvan Gaans-van den Brink, JMohammed, SHeck, Avan Els, CComprehensive analysis of the complex nature of the Human Leukocyte Antigen (HLA) class II ligandome is of utmost importance to understand the basis for CD4+ T cell mediated immunity and tolerance. Here, we implemented important improvements in the analysis of the repertoire of HLA-DR-presented peptides, using hybrid mass spectrometry-based peptide fragmentation techniques on a ligandome sample isolated from matured human monocyte-derived dendritic cells (DC). The reported data set constitutes nearly 14 thousand unique high-confident peptides, i.e. the largest single inventory of human DC derived HLA-DR ligands to date. From a technical viewpoint the most prominent finding is that no single peptide fragmentation technique could elucidate the majority of HLA-DR ligands, because of the wide range of physical chemical properties displayed by the HLA-DR ligandome. Our in-depth profiling allowed us to reveal a strikingly poor correlation between the source proteins identified in the HLA class II ligandome and the DC cellular proteome. Important selective sieving from the sampled proteome to the ligandome was evidenced by specificity in the sequences of the core regions both at their N- and C- termini, hence not only reflecting binding motifs but also dominant protease activity associated to the endolysosomal compartments. Moreover, we demonstrate that the HLA-DR ligandome reflects a surface representation of cell-compartments specific for biological events linked to the maturation of monocytes into antigen presenting cells. Our results present new perspectives into the complex nature of the HLA class II system and will aid future immunological studies in characterizing the full breadth of potential CD4+ T cell epitopes relevant in health and disease. |
| spellingShingle | Mommen, G Marino, F Meiring, H Poelen, M van Gaans-van den Brink, J Mohammed, S Heck, A van Els, C Sampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificity |
| title | Sampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificity |
| title_full | Sampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificity |
| title_fullStr | Sampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificity |
| title_full_unstemmed | Sampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificity |
| title_short | Sampling from the proteome to the human leukocyte antigen-DR (HLA-DR) ligandome proceeds via high specificity |
| title_sort | sampling from the proteome to the human leukocyte antigen dr hla dr ligandome proceeds via high specificity |
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