Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires
Human leukocyte antigen (HLA)-DR15 is a haplotype associated with multiple sclerosis. It contains the two DRB* genes DRB1*1501 (DR2b) and DRB5*0101 (DR2a). The reported anchor motif of the corresponding HLA-DR molecules was determined in 1994 based on a small number of peptide ligands and binding as...
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00984/full |
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| author | Erika Margaret Scholz Erika Margaret Scholz Miguel Marcilla Xavier Daura Xavier Daura David Arribas-Layton Eddie A. James Iñaki Alvarez Iñaki Alvarez |
| author_facet | Erika Margaret Scholz Erika Margaret Scholz Miguel Marcilla Xavier Daura Xavier Daura David Arribas-Layton Eddie A. James Iñaki Alvarez Iñaki Alvarez |
| author_sort | Erika Margaret Scholz |
| collection | DOAJ |
| description | Human leukocyte antigen (HLA)-DR15 is a haplotype associated with multiple sclerosis. It contains the two DRB* genes DRB1*1501 (DR2b) and DRB5*0101 (DR2a). The reported anchor motif of the corresponding HLA-DR molecules was determined in 1994 based on a small number of peptide ligands and binding assays. DR2a could display a set of peptides complementary to that presented by DR2b or, alternatively, a similar peptide repertoire but recognized in a different manner by T cells. It is known that DR2a and DR2b share some peptide ligands, although the degree of similarity of their associated peptidomes remains unclear. In addition, the contribution of each molecule to the global peptide repertoire presented by the HLA-DR15 haplotype has not been evaluated. We used mass spectrometry to analyze the peptide pools bound to DR2a and DR2b, identifying 169 and 555 unique peptide ligands of DR2a and DR2b, respectively. The analysis of these sets of peptides allowed the refinement of the corresponding binding motifs revealing novel anchor residues that had been overlooked in previous analyses. Moreover, the number of shared ligands between both molecules was low, indicating that DR2a and DR2b present complementary peptide repertoires to T cells. Finally, our analysis suggests that, quantitatively, both molecules contribute to the peptide repertoire presented by cells expressing the HLA-DR15 haplotype. |
| first_indexed | 2024-12-11T08:28:16Z |
| format | Article |
| id | doaj.art-57848a499f4a4942966a9254dc1a4bf5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T08:28:16Z |
| publishDate | 2017-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-57848a499f4a4942966a9254dc1a4bf52022-12-22T01:14:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.00984285906Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide RepertoiresErika Margaret Scholz0Erika Margaret Scholz1Miguel Marcilla2Xavier Daura3Xavier Daura4David Arribas-Layton5Eddie A. James6Iñaki Alvarez7Iñaki Alvarez8Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, SpainImmunology Unit, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, SpainProteomics Unit, Centro Nacional de Biotecnología (CSIC), Madrid, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, SpainCatalan Institution for Research and Advanced Studies (ICREA), Barcelona, SpainBenaroya Research Institute at Virginia Mason, Seattle, WA, United StatesBenaroya Research Institute at Virginia Mason, Seattle, WA, United StatesInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, SpainImmunology Unit, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, SpainHuman leukocyte antigen (HLA)-DR15 is a haplotype associated with multiple sclerosis. It contains the two DRB* genes DRB1*1501 (DR2b) and DRB5*0101 (DR2a). The reported anchor motif of the corresponding HLA-DR molecules was determined in 1994 based on a small number of peptide ligands and binding assays. DR2a could display a set of peptides complementary to that presented by DR2b or, alternatively, a similar peptide repertoire but recognized in a different manner by T cells. It is known that DR2a and DR2b share some peptide ligands, although the degree of similarity of their associated peptidomes remains unclear. In addition, the contribution of each molecule to the global peptide repertoire presented by the HLA-DR15 haplotype has not been evaluated. We used mass spectrometry to analyze the peptide pools bound to DR2a and DR2b, identifying 169 and 555 unique peptide ligands of DR2a and DR2b, respectively. The analysis of these sets of peptides allowed the refinement of the corresponding binding motifs revealing novel anchor residues that had been overlooked in previous analyses. Moreover, the number of shared ligands between both molecules was low, indicating that DR2a and DR2b present complementary peptide repertoires to T cells. Finally, our analysis suggests that, quantitatively, both molecules contribute to the peptide repertoire presented by cells expressing the HLA-DR15 haplotype.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00984/fullhuman leukocyte antigen-DRbinding motifmass spectrometrypeptidomemultiple sclerosis |
| spellingShingle | Erika Margaret Scholz Erika Margaret Scholz Miguel Marcilla Xavier Daura Xavier Daura David Arribas-Layton Eddie A. James Iñaki Alvarez Iñaki Alvarez Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires Frontiers in Immunology human leukocyte antigen-DR binding motif mass spectrometry peptidome multiple sclerosis |
| title | Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires |
| title_full | Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires |
| title_fullStr | Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires |
| title_full_unstemmed | Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires |
| title_short | Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires |
| title_sort | human leukocyte antigen hla drb1 15 01 and hla drb5 01 01 present complementary peptide repertoires |
| topic | human leukocyte antigen-DR binding motif mass spectrometry peptidome multiple sclerosis |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00984/full |
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