| Reference | ||
|---|---|---|
| Reference Type | Literature | IEDB_Reference:1037972 |
| Title | HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis. | |
| Authors | Jian Wang; Ivan Jelcic; Lena Mühlenbruch; Veronika Haunerdinger; Nora C Toussaint; Yingdong Zhao; Carolina Cruciani; Wolfgang Faigle; Reza Naghavian; Magdalena Foege; Thomas M C Binder; Thomas Eiermann; Lennart Opitz; Laura Fuentes-Font; Richard Reynolds; William W Kwok; Julie T Nguyen; Jar-How Lee; Andreas Lutterotti; Christian Münz; Hans-Georg Rammensee; Mathias Hauri-Hohl; Mireia Sospedra; Stefan Stevanovic; Roland Martin | |
| Affiliations | Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland; Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen 72076, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, Tübingen 72076, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen 72076, Germany; Pediatric Stem Cell Transplantation, University Children's Hospital Zurich, Zurich 8032, Switzerland; NEXUS Personalized Health Technologies, ETH Zurich, Zurich 8093, Switzerland; Swiss Institute of Bioinformatics, Zurich, Switzerland; Biometric Research Program, Division of Cancer Treatment and Diagnosis, NCI, NIH, Rockville, MD 20850, USA; HLA Laboratory of the Stefan Morsch Foundation (SMS), Birkenfeld 55765, Germany; Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany; Functional Genomics Center Zurich, Swiss Federal Institute of Technology and University of Zurich, Zurich 8057, Switzerland; Division of Neuroscience, Department of Brain Sciences, Imperial College London, ... | |
| Journal | Cell | |
| Year | 2020 | |
| Abstract | The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4<sup>+</sup> T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells. Furthermore, we identified autoreactive CD4<sup>+</sup> T cell clones that can cross-react with HLA-DR-derived self-peptides (HLA-DR-SPs), peptides from MS-associated foreign agents (Epstein-Barr virus and Akkermansia muciniphila), and autoantigens presented by DR2a and DR2b. Thus, both HLA-DR15 allomorphs jointly shape an autoreactive T cell repertoire by serving as antigen-presenting structures and epitope sources and by presenting the same foreign peptides and autoantigens to autoreactive CD4<sup>+</sup> T cells in MS. | |
| External Link | PXD015249 | |
| Curation Last Updated | 2021-06-15 20:01:32 | |
| Epitope | ||
|---|---|---|
| Epitope ID | 531678 | IEDB_epitope:531678 |
| Chemical Type | Linear peptide | |
| Linear Sequence | FDSDVGEYRAVTELGRPDA | |
| Source Molecule Name | HLA class II histocompatibility antigen, DRB1-1 beta chain precursor | |
| Source Organism | Homo sapiens (human) | |
| Starting Position | 69 | |
| Ending Position | 87 | |
| Epitope Reference Details | ||
|---|---|---|
| Epitope Structure Defines | Epitope containing region/antigenic site | |
| Epitope Name | Eluted Peptide 1889 | |
| Location of Data in Reference | Supplementary Table 2 | |
| In Vivo Processing | ||
|---|---|---|
| Host Organism | Homo sapiens (human) | |
| Host Details | ||
|---|---|---|
| Age | 25-54 years | |
| In Vivo Process | ||
|---|---|---|
| In Vivo Process Type | Occurrence of autoimmune disease | |
| Disease State | multiple sclerosis | |
| Disease Stage | Chronic; | OGMS:0000064 |
| Antigen Processing Comments | ||
|---|---|---|
| Antigen Processing Comments | B-cells and monocytes were collected from 3 untreated relapsing-remitting MS (RRMS) patients, and 3 RRMS patients treated with the anti-VLA4 antibody natalizumab (RRMS_NAT), aged 25-54; 4 males, 2 females. | |
| MHC Ligand Assay | ||
|---|---|---|
| Qualitative Measurement | Positive | |
| Method/Technique | cellular MHC/mass spectrometry | |
| Measurement of | ligand presentation | |
| Measurement Details | ||
|---|---|---|
| Number of Subjects Tested | 6 | |
| Number of Subjects Responded | 1 | |
| Antigen Presenting Cells | ||
|---|---|---|
| Cell Tissue Type | blood | |
| Cell Type | B cell | |
| Cell Culture Conditions | Direct Ex Vivo | |
| MHC Allele | ||
|---|---|---|
| MHC Allele Name | HLA-DRB5*01:01 | |
| MHC Evidence Code | Elution with MHC specific antibody | |
| MHC Ligand | ||
|---|---|---|
| Epitope Relation | Epitope | |
| Chemical Type | Linear peptide | |
| Linear Sequence | FDSDVGEYRAVTELGRPDA | |
| Source Molecule Name | HLA class II histocompatibility antigen, DRB1-1 beta chain precursor | |
| Source Organism | Homo sapiens (human) | |
| Starting Position | 69 | |
| Ending Position | 87 | |
| Assay Reference Details | ||
|---|---|---|
| Assay Comments by IEDB Curator | The epitope was eluted using an in-house generated anti-DR2a mAb. The response was positive in 1 of 3 RRMS patients treated with NAT. | |
| Location of Assay Data in Reference | Supplementary Table 2 | |