PMID- 27231714
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160527
LR  - 20181113
IS  - 2332-7812 (Print)
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 3
IP  - 4
DP  - 2016 Aug
TI  - Multiple sclerosis: Molecular mimicry of an antimyelin HLA class I restricted 
      T-cell receptor.
PG  - e241
LID - 10.1212/NXI.0000000000000241 [doi]
LID - e241
AB  - OBJECTIVE: To identify target antigens presented by human leukocyte antigen 
      (HLA)-A*02:01 to the myelin-reactive human T-cell receptor (TCR) 2D1, which was 
      originally isolated from a CD8+ T-cell clone recognizing proteolipid protein 
      (PLP) in the context of HLA-A*03:01, we employed a new antigen search technology. 
      METHODS: We used our recently developed antigen search technology that employs 
      plasmid-encoded combinatorial peptide libraries and a highly sensitive single 
      cell detection system to identify endogenous candidate peptides of mice and human 
      origin. We validated candidate antigens by independent T-cell assays using 
      synthetic peptides and refolded HLA:peptide complexes. A molecular model of 
      HLA-A*02:01:peptide complexes was obtained by molecular dynamics simulations. 
      RESULTS: We identified one peptide from glycerolphosphatidylcholine 
      phosphodiesterase 1, which is identical in mice and humans and originates from a 
      protein that is expressed in many cell types. When bound to HLA-A*02:01, this 
      peptide cross-stimulates the PLP-reactive HLA-A3-restricted TCR 2D1. 
      Investigation of molecular details revealed that the peptide length plays a 
      crucial role in its capacity to bind HLA-A*02:01 and to activate TCR 2D1. 
      Molecular modeling illustrated the 3D structures of activating HLA:peptide 
      complexes. CONCLUSIONS: Our results show that our antigen search technology 
      allows us to identify new candidate antigens of a presumably pathogenic, 
      autoreactive, human CD8+ T-cell-derived TCR. They further illustrate how this 
      TCR, which recognizes a myelin peptide bound to HLA-A*03:01, may cross-react with 
      an unrelated peptide presented by the protective HLA class I allele HLA-A*02:01.
FAU - Ruhl, Geraldine
AU  - Ruhl G
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Niedl, Anna G
AU  - Niedl AG
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Patronov, Atanas
AU  - Patronov A
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Siewert, Katherina
AU  - Siewert K
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Pinkert, Stefan
AU  - Pinkert S
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Kalemanov, Maria
AU  - Kalemanov M
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Friese, Manuel A
AU  - Friese MA
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Attfield, Kathrine E
AU  - Attfield KE
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Antes, Iris
AU  - Antes I
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Hohlfeld, Reinhard
AU  - Hohlfeld R
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
FAU - Dornmair, Klaus
AU  - Dornmair K
AD  - Institute of Clinical Neuroimmunology (G.R., A.G.N., K.S., R.H., K.D.) and Munich 
      Cluster for Systems Neurology (SyNergy) (R.H., K.D.), 
      Ludwig-Maximilian-University, Munich; Department of Life Sciences (A.P., M.K., 
      I.A.), Technical University Munich, Freising; Max Planck Institute of 
      Biochemistry (S.P.), Martinsried; Institute of Neuroimmunology and Multiple 
      Sclerosis (M.A.F.), University Medical Centre, Hamburg-Eppendorf, Hamburg, 
      Germany; MRC Human Immunology Unit (K.E.A.), Radcliffe Department of Medicine, 
      Weatherall, Institute of Molecular Medicine, University of Oxford, John Radcliffe 
      Hospital, UK; and Center for Integrated Protein Science Munich (CIPSM) (I.A.), 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20160517
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
PMC - PMC4871805
EDAT- 2016/05/28 06:00
MHDA- 2016/05/28 06:01
PMCR- 2016/05/17
CRDT- 2016/05/28 06:00
PHST- 2016/01/20 00:00 [received]
PHST- 2016/04/01 00:00 [accepted]
PHST- 2016/05/28 06:00 [entrez]
PHST- 2016/05/28 06:00 [pubmed]
PHST- 2016/05/28 06:01 [medline]
PHST- 2016/05/17 00:00 [pmc-release]
AID - NEURIMMINFL2016009134 [pii]
AID - 10.1212/NXI.0000000000000241 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2016 May 17;3(4):e241. doi: 
      10.1212/NXI.0000000000000241. eCollection 2016 Aug.