Dataset Information

In Silico Prediction Analysis of Idiotope-Driven T-B Cell Collaboration in Multiple Sclerosis.

ABSTRACT: Memory B cells acting as antigen-presenting cells are believed to be important in multiple sclerosis (MS), but the antigen they present remains unknown. We hypothesized that B cells may activate CD4+ T cells in the central nervous system of MS patients by presenting idiotopes from their own immunoglobulin variable regions on human leukocyte antigen (HLA) class II molecules. Here, we use bioinformatics prediction analysis of B cell immunoglobulin variable regions from 11 MS patients and 6 controls with other inflammatory neurological disorders (OINDs), to assess whether the prerequisites for such idiotope-driven T-B cell collaboration are present. Our findings indicate that idiotopes from the complementarity determining region (CDR) 3 of MS patients on average have high predicted affinities for disease associated HLA-DRB1*15:01 molecules and are predicted to be endosomally processed by cathepsin S and L in positions that allows such HLA binding to occur. Additionally, complementarity determining region 3 sequences from cerebrospinal fluid (CSF) B cells from MS patients contain on average more rare T cell-exposed motifs that could potentially escape tolerance and stimulate CD4+ T cells than CSF B cells from OIND patients. Many of these features were associated with preferential use of the IGHV4 gene family by CSF B cells from MS patients. This is the first study to combine high-throughput sequencing of patient immune repertoires with large-scale prediction analysis and provides key indicators for future in vitro and in vivo analyses.

SUBMITTER: Hoglund RA

PROVIDER: S-EPMC5630699 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

<i>In Silico</i> Prediction Analysis of Idiotope-Driven T-B Cell Collaboration in Multiple Sclerosis.

Høglund Rune A RA Lossius Andreas A Johansen Jorunn N JN Homan Jane J Benth Jūratė Šaltytė JŠ Robins Harlan H Bogen Bjarne B Bremel Robert D RD Holmøy Trygve T

Frontiers in immunology 20171002

Memory B cells acting as antigen-presenting cells are believed to be important in multiple sclerosis (MS), but the antigen they present remains unknown. We hypothesized that B cells may activate CD4<sup>+</sup> T cells in the central nervous system of MS patients by presenting idiotopes from their own immunoglobulin variable regions on human leukocyte antigen (HLA) class II molecules. Here, we use bioinformatics prediction analysis of B cell immunoglobulin variable regions from 11 MS patients an ...[more]

PMID: 29038659

Similar Datasets

Project description:BACKGROUND:Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade. OBJECTIVES:The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis. MATERIALS AND METHODS:As there wasn't any tertiary structure of PLP available in the Protein Data Bank (PDB) and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective in silico, was performed to fi nd PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens (HLA). The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms. RESULTS:Three common regions, AA58-74, AA161-177, and AA238-254 were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA58-74 in bacteria showed a similar peptide in bacteria (mainly consistent with that of clostridium and mycobacterium) and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS. CONCLUSIONS:Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally (in vitro). In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable results for researches in a shorter time and at a lower cost.

Dataset Information

In Silico Prediction Analysis of Idiotope-Driven T-B Cell Collaboration in Multiple Sclerosis.

Publications

<i>In Silico</i> Prediction Analysis of Idiotope-Driven T-B Cell Collaboration in Multiple Sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets