Dataset Information

HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

ABSTRACT: Autoimmune diseases are often associated with HLA molecules. Multiple sclerosis (MS) is a prototypical example with the HLA-DR15 haplotype as strongest genetic factor. How it contributes to MS is not clear, but key to understand this and other autoimmune diseases. Autoreactive CD4+ T cells and proinflammatory B cells are central pathogenetic factors, and since HLA-DR molecules present peptides to CD4+ T cells, we characterized the peptidomes of the two HLA-DR15 allomorphs DR2a and DR2b on B cells. Self-peptides from HLA-DR α- and β-chains themselves are abundantly presented on B cells. We identified autoreactive CD4+ T cell clones, which recognize HLA-DR-derived self-peptides and peptides from the MS-related infectious agents EBV and Akkermansia and the autoantigen RAS guanyl-releasing protein 2. Our data demonstrate how the two MS-associated HLA-DR15 allomorphs function as antigen-presenting structures and source of peptides during peripheral maintenance of autoreactive T cells and activation by MS-associated pathogens.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Monocyte, Blood

DISEASE(S): Multiple Sclerosis

SUBMITTER: Lena Mühlenbruch

LAB HEAD: Stefan Stevanović

PROVIDER: PXD015249 | Pride | 2020-10-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	HD-1_Bcells_DR2a_Rep-1.msf	Msf
	HD-1_Bcells_DR2a_Rep-1.raw	Raw
	HD-1_Bcells_DR2a_Rep-2.msf	Msf
	HD-1_Bcells_DR2a_Rep-2.raw	Raw
	HD-1_Bcells_DR2a_Rep-3.msf	Msf

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HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis.

Wang Jian J Jelcic Ivan I Mühlenbruch Lena L Haunerdinger Veronika V Toussaint Nora C NC Zhao Yingdong Y Cruciani Carolina C Faigle Wolfgang W Naghavian Reza R Foege Magdalena M Binder Thomas M C TMC Eiermann Thomas T Opitz Lennart L Fuentes-Font Laura L Reynolds Richard R Kwok William W WW Nguyen Julie T JT Lee Jar-How JH Lutterotti Andreas A Münz Christian C Rammensee Hans-Georg HG Hauri-Hohl Mathias M Sospedra Mireia M Stevanovic Stefan S Martin Roland R

Cell 20201021 5

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 ...[more]

PMID: 33091337

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