PMID- 29038659
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - In Silico Prediction Analysis of Idiotope-Driven T-B Cell Collaboration in 
      Multiple Sclerosis.
PG  - 1255
LID - 10.3389/fimmu.2017.01255 [doi]
LID - 1255
AB  - 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.
FAU - Hoglund, Rune A
AU  - Hoglund RA
AD  - Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
FAU - Lossius, Andreas
AU  - Lossius A
AD  - Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
AD  - Faculty of Medicine, Department of Immunology and Transfusion Medicine, 
      University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
FAU - Johansen, Jorunn N
AU  - Johansen JN
AD  - Faculty of Medicine, Department of Immunology and Transfusion Medicine, 
      University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
FAU - Homan, Jane
AU  - Homan J
AD  - EigenBio LLC, Madison, WI, United States.
FAU - Benth, Jurate Saltyte
AU  - Benth JS
AD  - Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
AD  - Health Services Research Unit, Akershus University Hospital, Lorenskog, Norway.
FAU - Robins, Harlan
AU  - Robins H
AD  - Adaptive Biotechnologies, Seattle, WA, United States.
FAU - Bogen, Bjarne
AU  - Bogen B
AD  - Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
AD  - Faculty of Medicine, Department of Immunology and Transfusion Medicine, 
      University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
AD  - Centre for Immune Regulation, University of Oslo, Oslo, Norway.
FAU - Bremel, Robert D
AU  - Bremel RD
AD  - EigenBio LLC, Madison, WI, United States.
FAU - Holmoy, Trygve
AU  - Holmoy T
AD  - Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
LA  - eng
SI  - figshare/10.6084/m9.figshare.5035703
SI  - Dryad/10.5061/dryad.35ks2
PT  - Journal Article
DEP - 20171002
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5630699
OTO - NOTNLM
OT  - B cell
OT  - T cell
OT  - bioinformatics
OT  - idiotope
OT  - immunoglobulin
OT  - immunoglobulin heavy variable
OT  - immunosequencing
OT  - multiple sclerosis
EDAT- 2017/10/19 06:00
MHDA- 2017/10/19 06:01
PMCR- 2017/01/01
CRDT- 2017/10/18 06:00
PHST- 2017/05/26 00:00 [received]
PHST- 2017/09/20 00:00 [accepted]
PHST- 2017/10/18 06:00 [entrez]
PHST- 2017/10/19 06:00 [pubmed]
PHST- 2017/10/19 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.01255 [doi]
PST - epublish
SO  - Front Immunol. 2017 Oct 2;8:1255. doi: 10.3389/fimmu.2017.01255. eCollection 
      2017.