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PDBsum entry 1h15

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protein ligands Protein-protein interface(s) links
Immune system/transferase PDB id
1h15
Jmol
Contents
Protein chains
180 a.a. *
189 a.a. *
14 a.a. *
Ligands
NAG-NAG
NAG ×3
Waters ×30
* Residue conservation analysis
PDB id:
1h15
Name: Immune system/transferase
Title: X-ray crystal structure of hla-dra1 0101/Drb5 0101 Complexed with a peptide from epstein barr virus DNA polymerase
Structure: Hla class ii histocompatibility antigen, dr alpha chain. Chain: a, d. Fragment: alpha chain, residues 26-207. Synonym: hla-dra, major histocompatibility complex a chain. Engineered: yes. Hla class ii histocompatibility antigen, dr beta 1 chain. Chain: b, e.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: s2. Synthetic: yes. Human herpesvirus 4. Epstein barr virus.
Biol. unit: Trimer (from PDB file)
Resolution:
3.10Å     R-factor:   0.256     R-free:   0.310
Authors: H.Lang,H.Jacobsen,S.Ikemizu,C.Andersson,K.Harlos,L.Madsen, P.Hjorth,L.Sondergaard,A.Svejgaard,K.Wucherpfennig, D.I.Stuart,J.I.Bell,E.Y.Jones,L.Fugger
Key ref:
H.L.Lang et al. (2002). A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol, 3, 940-943. PubMed id: 12244309 DOI: 10.1038/ni835
Date:
02-Jul-02     Release date:   03-Oct-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
Seq:
Struc:
254 a.a.
180 a.a.
Protein chains
Pfam   ArchSchema ?
Q30154  (DRB5_HUMAN) -  HLA class II histocompatibility antigen, DR beta 5 chain
Seq:
Struc:
266 a.a.
189 a.a.
Protein chains
Pfam   ArchSchema ?
P03198  (DPOL_EBVB9) -  DNA polymerase catalytic subunit
Seq:
Struc:
 
Seq:
Struc:
1015 a.a.
14 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains C, F: E.C.2.7.7.7  - DNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Deoxynucleoside triphosphate
+ DNA(n)
= diphosphate
+ DNA(n+1)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 

 

 
    reference    
 
 
DOI no: 10.1038/ni835 Nat Immunol 3:940-943 (2002)
PubMed id: 12244309  
 
 
A functional and structural basis for TCR cross-reactivity in multiple sclerosis.
H.L.Lang, H.Jacobsen, S.Ikemizu, C.Andersson, K.Harlos, L.Madsen, P.Hjorth, L.Sondergaard, A.Svejgaard, K.Wucherpfennig, D.I.Stuart, J.I.Bell, E.Y.Jones, L.Fugger.
 
  ABSTRACT  
 
The multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may influence susceptibility to MS. We demonstrate that a T cell receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV peptide complex revealed a marked degree of structural equivalence to the DRB1*1501-MBP peptide complex at the surface presented for TCR recognition. This provides structural evidence for molecular mimicry involving HLA molecules. The structural details suggest an explanation for the preponderance of MHC class II associations in HLA-associated diseases.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structural comparisons. (a) The EBV peptide is drawn in green with F[o] - F[c] omit map shown as a semitransparent surface contoured at 2 . (b) Superposition of EBV (green) and MBP (red) peptides based on MHC class II structures. Solvent-exposed residues critical for Hy.2E11 TCR recognition are labeled in black. (c) Alignment of EBV(627 -641) and MBP(87 -99) in their MHC class II binding registers. Anchor residues and solvent-exposed residues required for Hy.2E11 stimulation are outlined in yellow, and vertical bars indicate importance to T cell recognition. (d) Superposed C traces of the HLA-DRB5*0101 -EBV (green), HLA-DRB1*1501 -MBP (red) and HLA-DRB5*0101 -MBP (blue) complexes. Differences in B64 -B67 are due to lattice contacts in the HLA-DRB5*0101 -EBV crystal and reveal an inherent flexibility in this region of the MHC class II structure.
Figure 3.
Figure 3. The TCR recognition surface. (a) Symbolic representations of the DRB1*1501-MBP, DRB5*0101-MBP and DRB5*0101-EBV complexes. The critical peptide residues are represented as a triangle (valine), rectangle (lysine), pentagon (histidine) and hexagon (phenylalanine). (b) Ribbon representation of the HLA-DRB5*0101 -EBV complex, colored according to differences in the structural superposition with HLA-DRB1*1501 -MBP. Regions in green show least variation, whereas those in red show the greatest changes. The C positions of P-1 valine, P2 histidine, P3 phenylalanine and P5 lysine are represented as in a, and P7 histidine by a sphere. The putative TCR binding footprint is represented as a semitransparent surface in pink and blue for the and chains, respectively. Structural mimicry is particularly strong within the TCR chain -binding footprint, in line with observations on the primary importance of this region for TCR binding36.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2002, 3, 940-943) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20936290 A.Alter, A.Grant, L.Abel, A.Alcaïs, and E.Schurr (2011).
Leprosy as a genetic disease.
  Mamm Genome, 22, 19-31.  
21510932 B.Bartok, and G.J.Silverman (2011).
Development of anti-CD20 therapy for multiple sclerosis.
  Exp Cell Res, 317, 1312-1318.  
21280120 B.Loll, C.Rückert, C.S.Hee, W.Saenger, B.Uchanska-Ziegler, and A.Ziegler (2011).
Loss of recognition by cross-reactive T cells and its relation to a C-terminus-induced conformational reorientation of an HLA-B*2705-bound peptide.
  Protein Sci, 20, 278-290.
PDB code: 3lv3
21543847 R.M.McMahon, L.Friis, C.Siebold, M.A.Friese, L.Fugger, and E.Y.Jones (2011).
Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis.
  Acta Crystallogr D Biol Crystallogr, 67, 447-454.
PDB code: 2xpg
20369303 A.Ascherio, and K.L.Munger (2010).
Epstein-barr virus infection and multiple sclerosis: a review.
  J Neuroimmune Pharmacol, 5, 271-277.  
20415861 A.Ascherio, and K.L.Munger (2010).
99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: Epstein-Barr virus and multiple sclerosis: epidemiological evidence.
  Clin Exp Immunol, 160, 120-124.  
20157307 A.E.Handel, G.Giovannoni, G.C.Ebers, and S.V.Ramagopalan (2010).
Environmental factors and their timing in adult-onset multiple sclerosis.
  Nat Rev Neurol, 6, 156-166.  
20303880 C.K.Glass, K.Saijo, B.Winner, M.C.Marchetto, and F.H.Gage (2010).
Mechanisms underlying inflammation in neurodegeneration.
  Cell, 140, 918-934.  
20225292 I.A.van der Mei, A.L.Ponsonby, B.V.Taylor, J.Stankovich, J.L.Dickinson, S.Foote, A.Kemp, and T.Dwyer (2010).
Human leukocyte antigen-DR15, low infant sibling exposure and multiple sclerosis: gene-environment interaction.
  Ann Neurol, 67, 261-265.  
20187864 K.Lauer (2010).
Environmental risk factors in multiple sclerosis.
  Expert Rev Neurother, 10, 421-440.  
20603280 K.Rejdak, S.Jackson, and G.Giovannoni (2010).
Multiple sclerosis: a practical overview for clinicians.
  Br Med Bull, 95, 79.  
20714779 T.Scheikl, B.Pignolet, L.T.Mars, and R.S.Liblau (2010).
Transgenic mouse models of multiple sclerosis.
  Cell Mol Life Sci, 67, 4011-4034.  
  20029463 Y.Zhao, and X.Li (2010).
Cross-immune tolerance: conception and its potential significance on transplantation tolerance.
  Cell Mol Immunol, 7, 20-25.  
19664371 B.A.Bagert (2009).
Epstein-barr virus in multiple sclerosis.
  Curr Neurol Neurosci Rep, 9, 405-410.  
19319143 C.Münz, J.D.Lünemann, M.T.Getts, and S.D.Miller (2009).
Antiviral immune responses: triggers of or triggered by autoimmunity?
  Nat Rev Immunol, 9, 246-258.  
19444307 J.Goverman (2009).
Autoimmune T cell responses in the central nervous system.
  Nat Rev Immunol, 9, 393-407.  
19303388 M.Harkiolaki, S.L.Holmes, P.Svendsen, J.W.Gregersen, L.T.Jensen, R.McMahon, M.A.Friese, G.van Boxel, R.Etzensperger, J.S.Tzartos, K.Kranc, S.Sainsbury, K.Harlos, E.D.Mellins, J.Palace, M.M.Esiri, P.A.van der Merwe, E.Y.Jones, and L.Fugger (2009).
T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.
  Immunity, 30, 348-357.
PDB code: 2wbj
19672899 R.Hohlfeld (2009).
Multiple sclerosis: human model for EAE?
  Eur J Immunol, 39, 2036-2039.  
19286671 S.E.Baranzini, N.W.Galwey, J.Wang, P.Khankhanian, R.Lindberg, D.Pelletier, W.Wu, B.M.Uitdehaag, L.Kappos, C.H.Polman, P.M.Matthews, S.L.Hauser, R.A.Gibson, J.R.Oksenberg, and M.R.Barnes (2009).
Pathway and network-based analysis of genome-wide association studies in multiple sclerosis.
  Hum Mol Genet, 18, 2078-2090.  
19387341 S.V.Ramagopalan, J.C.Knight, and G.C.Ebers (2009).
Multiple sclerosis and the major histocompatibility complex.
  Curr Opin Neurol, 22, 219-225.  
18970977 A.Compston, and A.Coles (2008).
Multiple sclerosis.
  Lancet, 372, 1502-1517.  
18199740 A.Geluk, J.van der Ploeg, R.O.Teles, K.L.Franken, C.Prins, J.W.Drijfhout, E.N.Sarno, E.P.Sampaio, and T.H.Ottenhoff (2008).
Rational combination of peptides derived from different Mycobacterium leprae proteins improves sensitivity for immunodiagnosis of M. leprae infection.
  Clin Vaccine Immunol, 15, 522-533.  
18701576 A.K.Tai, E.J.O'Reilly, K.A.Alroy, K.C.Simon, K.L.Munger, B.T.Huber, and A.Ascherio (2008).
Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis.
  Mult Scler, 14, 1175-1180.  
18461312 A.Svejgaard (2008).
The immunogenetics of multiple sclerosis.
  Immunogenetics, 60, 275-286.  
18763026 C.M.Costantino, C.Baecher-Allan, and D.A.Hafler (2008).
Multiple sclerosis and regulatory T cells.
  J Clin Immunol, 28, 697-706.  
18155234 C.McBeth, A.Seamons, J.C.Pizarro, S.J.Fleishman, D.Baker, T.Kortemme, J.M.Goverman, and R.K.Strong (2008).
A new twist in TCR diversity revealed by a forbidden alphabeta TCR.
  J Mol Biol, 375, 1306-1319.
PDB codes: 2p1y 2p24
18703007 D.Franciotta, M.Salvetti, F.Lolli, B.Serafini, and F.Aloisi (2008).
B cells and multiple sclerosis.
  Lancet Neurol, 7, 852-858.  
18663124 J.D.Lünemann, I.Jelcić, S.Roberts, A.Lutterotti, B.Tackenberg, R.Martin, and C.Münz (2008).
EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-gamma and IL-2.
  J Exp Med, 205, 1763-1773.  
  18713991 K.Kawamura, K.A.McLaughlin, R.Weissert, and T.G.Forsthuber (2008).
Myelin-reactive type B T cells and T cells specific for low-affinity MHC-binding myelin peptides escape tolerance in HLA-DR transgenic mice.
  J Immunol, 181, 3202-3211.  
17713752 K.Ruprecht (2008).
[Multiple sclerosis and Epstein-Barr virus : new developments and perspectives]
  Nervenarzt, 79, 399-407.  
18492786 L.Li, B.Wang, J.A.Frelinger, and R.Tisch (2008).
T-cell promiscuity in autoimmune diabetes.
  Diabetes, 57, 2099-2106.  
18425726 P.Stinissen, and N.Hellings (2008).
Activation of myelin reactive T cells in multiple sclerosis: a possible role for T cell degeneracy?
  Eur J Immunol, 38, 1190-1193.  
18513924 R.Etzensperger, R.M.McMahon, E.Y.Jones, and L.Fugger (2008).
Dissection of the multiple sclerosis associated DR2 haplotype.
  J Autoimmun, 31, 201-207.  
18550621 S.Jilek, M.Schluep, P.Meylan, F.Vingerhoets, L.Guignard, A.Monney, J.Kleeberg, G.Le Goff, G.Pantaleo, and R.A.Du Pasquier (2008).
Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis.
  Brain, 131, 1712-1721.  
17444504 A.Ascherio, and K.L.Munger (2007).
Environmental risk factors for multiple sclerosis. Part I: the role of infection.
  Ann Neurol, 61, 288-299.  
20477676 A.N.Khitrov, Z.S.Shogenov, E.B.Tretyak, A.I.Ischenko, E.Matsuura, O.Neuhaus, M.A.Paltsev, and S.V.Suchkov (2007).
Postinfectious immunodeficiency and autoimmunity: pathogenic and clinical values and implications.
  Expert Rev Clin Immunol, 3, 323-331.  
17559580 B.E.Hansen, A.H.Rasmussen, B.K.Jakobsen, L.P.Ryder, and A.Svejgaard (2007).
Extraordinary cross-reactivity of an autoimmune T-cell receptor recognizing specific peptides both on autologous and on allogeneic HLA class II molecules.
  Tissue Antigens, 70, 42-52.  
17984305 B.Serafini, B.Rosicarelli, D.Franciotta, R.Magliozzi, R.Reynolds, P.Cinque, L.Andreoni, P.Trivedi, M.Salvetti, A.Faggioni, and F.Aloisi (2007).
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain.
  J Exp Med, 204, 2899-2912.  
17521918 C.Mazza, and B.Malissen (2007).
What guides MHC-restricted TCR recognition?
  Semin Immunol, 19, 225-235.  
17495618 G.Giovannoni, and G.Ebers (2007).
Multiple sclerosis: the environment and causation.
  Curr Opin Neurol, 20, 261-268.  
17497145 G.P.Bondinas, A.K.Moustakas, and G.K.Papadopoulos (2007).
The spectrum of HLA-DQ and HLA-DR alleles, 2006: a listing correlating sequence and structure with function.
  Immunogenetics, 59, 539-553.  
17488592 J.D.Lünemann, and C.Münz (2007).
Epstein-Barr virus and multiple sclerosis.
  Curr Neurol Neurosci Rep, 7, 253-258.  
17459939 J.D.Lünemann, T.Kamradt, R.Martin, and C.Münz (2007).
Epstein-barr virus: environmental trigger of multiple sclerosis?
  J Virol, 81, 6777-6784.  
17514718 J.I.Greenstein (2007).
Current concepts of the cellular and molecular pathophysiology of multiple sclerosis.
  Dev Neurobiol, 67, 1248-1265.  
20477024 K.L.Munger, and A.Ascherio (2007).
Risk factors in the development of multiple sclerosis.
  Expert Rev Clin Immunol, 3, 739-748.  
17385083 M.L.Opsahl, and P.G.Kennedy (2007).
An attempt to investigate the presence of Epstein Barr virus in multiple sclerosis and normal control brain tissue.
  J Neurol, 254, 425-430.  
17230443 N.Larke, E.J.Im, R.Wagner, C.Williamson, A.L.Williamson, A.J.McMichael, and T.Hanke (2007).
Combined single-clade candidate HIV-1 vaccines induce T cell responses limited by multiple forms of in vivo immune interference.
  Eur J Immunol, 37, 566-577.  
17917546 O.Barzilai, M.Ram, and Y.Shoenfeld (2007).
Viral infection can induce the production of autoantibodies.
  Curr Opin Rheumatol, 19, 636-643.  
17207708 R.J.Duquesnoy, and M.Askar (2007).
HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP.
  Hum Immunol, 68, 12-25.  
17850581 T.Holmøy, and F.Vartdal (2007).
The immunological basis for treatment of multiple sclerosis.
  Scand J Immunol, 66, 374-382.  
16537438 A.A.Musse, J.M.Boggs, and G.Harauz (2006).
Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope.
  Proc Natl Acad Sci U S A, 103, 4422-4427.  
16221670 C.Rückert, M.T.Fiorillo, B.Loll, R.Moretti, J.Biesiadka, W.Saenger, A.Ziegler, R.Sorrentino, and B.Uchanska-Ziegler (2006).
Conformational dimorphism of self-peptides and molecular mimicry in a disease-associated HLA-B27 subtype.
  J Biol Chem, 281, 2306-2316.
PDB code: 2a83
17013988 E.J.Im, J.P.Nkolola, K.di Gleria, A.J.McMichael, and T.Hanke (2006).
Induction of long-lasting multi-specific CD8+ T cells by a four-component DNA-MVA/HIVA-RENTA candidate HIV-1 vaccine in rhesus macaques.
  Eur J Immunol, 36, 2574-2584.  
16502434 E.L.Thacker, F.Mirzaei, and A.Ascherio (2006).
Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis.
  Ann Neurol, 59, 499-503.  
16557259 E.Y.Jones, L.Fugger, J.L.Strominger, and C.Siebold (2006).
MHC class II proteins and disease: a structural perspective.
  Nat Rev Immunol, 6, 271-282.  
16757604 F.C.Westall (2006).
Molecular mimicry revisited: gut bacteria and multiple sclerosis.
  J Clin Microbiol, 44, 2099-2104.  
16987736 G.Giovannoni, G.R.Cutter, J.Lunemann, R.Martin, C.Münz, S.Sriram, I.Steiner, M.R.Hammerschlag, and C.A.Gaydos (2006).
Infectious causes of multiple sclerosis.
  Lancet Neurol, 5, 887-894.  
16963442 J.K.Archbold, W.A.Macdonald, J.J.Miles, R.M.Brennan, L.Kjer-Nielsen, J.McCluskey, S.R.Burrows, and J.Rossjohn (2006).
Alloreactivity between disparate cognate and allogeneic pMHC-I complexes is the result of highly focused, peptide-dependent structural mimicry.
  J Biol Chem, 281, 34324-34332.
PDB code: 2h6p
17006452 J.W.Gregersen, K.R.Kranc, X.Ke, P.Svendsen, L.S.Madsen, A.R.Thomsen, L.R.Cardon, J.I.Bell, and L.Fugger (2006).
Functional epistasis on a common MHC haplotype associated with multiple sclerosis.
  Nature, 443, 574-577.  
16455578 L.McCoy, I.Tsunoda, and R.S.Fujinami (2006).
Multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation.
  Autoimmunity, 39, 9.  
16518843 M.C.Alcaro, and A.M.Papini (2006).
Contribution of peptides to multiple sclerosis research.
  Biopolymers, 84, 349-367.  
  16424227 M.Sospedra, P.A.Muraro, I.Stefanová, Y.Zhao, K.Chung, Y.Li, M.Giulianotti, R.Simon, R.Mariuzza, C.Pinilla, and R.Martin (2006).
Redundancy in antigen-presenting function of the HLA-DR and -DQ molecules in the multiple sclerosis-associated HLA-DR2 haplotype.
  J Immunol, 176, 1951-1961.  
16455577 M.Sospedra, and R.Martin (2006).
Molecular mimicry in multiple sclerosis.
  Autoimmunity, 39, 3-8.  
17010587 M.Sospedra, and R.Martin (2006).
When T cells recognize a pattern, they might cause trouble.
  Curr Opin Immunol, 18, 697-703.  
16927411 S.Haahr, and P.Höllsberg (2006).
Multiple sclerosis is linked to Epstein-Barr virus infection.
  Rev Med Virol, 16, 297-310.  
16021348 S.Sotgiu, M.Pugliatti, M.A.Sotgiu, M.L.Fois, G.Arru, A.Sanna, and G.Rosati (2006).
Seasonal fluctuation of multiple sclerosis births in Sardinia.
  J Neurol, 253, 38-44.  
16761313 V.Appay, D.E.Speiser, N.Rufer, S.Reynard, C.Barbey, J.C.Cerottini, S.Leyvraz, C.Pinilla, and P.Romero (2006).
Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.
  Eur J Immunol, 36, 1805-1814.  
15661092 A.Bar-Or (2005).
Immunology of multiple sclerosis.
  Neurol Clin, 23, 149.  
16033693 A.Cox, A.Coles, N.Antoun, O.Malik, C.Lucchinnetti, and A.Compston (2005).
Recurrent myelitis and optic neuritis in a 29-year-old woman.
  Lancet Neurol, 4, 510-516.  
20411047 A.J.Adler (2005).
Peripheral Tolerization of Effector and Memory T Cells: Implications for Autoimmunity and Tumor-Immunity.
  Curr Immunol Rev, 1, 21-28.  
15531581 B.Laugel, J.M.Boulter, N.Lissin, A.Vuidepot, Y.Li, E.Gostick, L.E.Crotty, D.C.Douek, J.Hemelaar, D.A.Price, B.K.Jakobsen, and A.K.Sewell (2005).
Design of soluble recombinant T cell receptors for antigen targeting and T cell inhibition.
  J Biol Chem, 280, 1882-1892.  
16170080 D.Buljevac, G.J.van Doornum, H.Z.Flach, J.Groen, A.D.Osterhaus, W.Hop, P.A.van Doorn, F.G.van der Meché, and R.Q.Hintzen (2005).
Epstein-Barr virus and disease activity in multiple sclerosis.
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16254700 H.P.Hartung, B.C.Kieseier, and B.Hemmer (2005).
Purely systemically active anti-inflammatory treatments are adequate to control multiple sclerosis.
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15843798 I.A.Wilson, and R.L.Stanfield (2005).
MHC restriction: slip-sliding away.
  Nat Immunol, 6, 434-435.  
16282464 I.Tsunoda, L.Q.Kuang, M.Kobayashi-Warren, and R.S.Fujinami (2005).
Central nervous system pathology caused by autoreactive CD8+ T-cell clones following virus infection.
  J Virol, 79, 14640-14646.  
15664161 J.Maynard, K.Petersson, D.H.Wilson, E.J.Adams, S.E.Blondelle, M.J.Boulanger, D.B.Wilson, and K.C.Garcia (2005).
Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity.
  Immunity, 22, 81-92.
PDB code: 1u3h
15771584 M.Sospedra, and R.Martin (2005).
Immunology of multiple sclerosis.
  Annu Rev Immunol, 23, 683-747.  
15537660 M.T.Fiorillo, C.Rückert, M.Hülsmeyer, R.Sorrentino, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2005).
Allele-dependent similarity between viral and self-peptide presentation by HLA-B27 subtypes.
  J Biol Chem, 280, 2962-2971.
PDB codes: 1uxs 1uxw
16189211 P.Ballabh, F.Hu, M.Kumarasiri, A.Braun, and M.Nedergaard (2005).
Development of tight junction molecules in blood vessels of germinal matrix, cerebral cortex, and white matter.
  Pediatr Res, 58, 791-798.  
16281923 P.Höllsberg, M.Kusk, E.Bech, H.J.Hansen, J.Jakobsen, and S.Haahr (2005).
Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity.
  Acta Neurol Scand, 112, 395-402.  
  15841210 S.Cepok, D.Zhou, R.Srivastava, S.Nessler, S.Stei, K.Büssow, N.Sommer, and B.Hemmer (2005).
Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis.
  J Clin Invest, 115, 1352-1360.  
15782388 T.Christensen (2005).
Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses.
  Rev Med Virol, 15, 179-211.  
15847838 T.Holmøy, and F.Vartdal (2005).
Infectious causes of multiple sclerosis.
  Lancet Neurol, 4, 268; discussion 269.  
15963251 T.Magnus, and M.S.Rao (2005).
Neural stem cells in inflammatory CNS diseases: mechanisms and therapy.
  J Cell Mol Med, 9, 303-319.  
15845547 T.Sandalova, J.Michaëlsson, R.A.Harris, J.Odeberg, G.Schneider, K.Kärre, and A.Achour (2005).
A structural basis for CD8+ T cell-dependent recognition of non-homologous peptide ligands: implications for molecular mimicry in autoreactivity.
  J Biol Chem, 280, 27069-27075.
PDB code: 1zhb
16268663 W.A.Sheremata, A.Minagar, J.S.Alexander, and T.Vollmer (2005).
The role of alpha-4 integrin in the aetiology of multiple sclerosis: current knowledge and therapeutic implications.
  CNS Drugs, 19, 909-922.  
16079912 Y.Li, Y.Huang, J.Lue, J.A.Quandt, R.Martin, and R.A.Mariuzza (2005).
Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule.
  EMBO J, 24, 2968-2979.
PDB code: 1zgl
15276395 A.M.Risitano, J.P.Maciejewski, S.Green, M.Plasilova, W.Zeng, and N.S.Young (2004).
In-vivo dominant immune responses in aplastic anaemia: molecular tracking of putatively pathogenetic T-cell clones by TCR beta-CDR3 sequencing.
  Lancet, 364, 355-364.  
15228754 A.Minagar, E.G.Toledo, J.S.Alexander, and R.E.Kelley (2004).
Pathogenesis of brain and spinal cord atrophy in multiple sclerosis.
  J Neuroimaging, 14, 5S.  
  15509529 C.Teuscher, J.Y.Bunn, P.D.Fillmore, R.J.Butterfield, J.F.Zachary, and E.P.Blankenhorn (2004).
Gender, age, and season at immunization uniquely influence the genetic control of susceptibility to histopathological lesions and clinical signs of experimental allergic encephalomyelitis: implications for the genetics of multiple sclerosis.
  Am J Pathol, 165, 1593-1602.  
15102364 C.W.Ang, B.C.Jacobs, and J.D.Laman (2004).
The Guillain-Barré syndrome: a true case of molecular mimicry.
  Trends Immunol, 25, 61-66.  
14726460 E.L.Oleszak, J.R.Chang, H.Friedman, C.D.Katsetos, and C.D.Platsoucas (2004).
Theiler's virus infection: a model for multiple sclerosis.
  Clin Microbiol Rev, 17, 174-207.  
15150306 H.Hjalgrim, S.Rasmussen, K.Rostgaard, N.M.Nielsen, N.Koch-Henriksen, L.Munksgaard, H.H.Storm, and M.Melbye (2004).
Familial clustering of Hodgkin lymphoma and multiple sclerosis.
  J Natl Cancer Inst, 96, 780-784.  
14871644 J.C.Prinz (2004).
Disease mimicry--a pathogenetic concept for T cell-mediated autoimmune disorders triggered by molecular mimicry?
  Autoimmun Rev, 3, 10-15.  
15583017 J.K.Lee, G.Stewart-Jones, T.Dong, K.Harlos, K.Di Gleria, L.Dorrell, D.C.Douek, P.A.van der Merwe, E.Y.Jones, and A.J.McMichael (2004).
T cell cross-reactivity and conformational changes during TCR engagement.
  J Exp Med, 200, 1455-1466.
PDB codes: 2bsu 2bsv 2v2w 2v2x
15104670 J.W.Gregersen, S.Holmes, and L.Fugger (2004).
Humanized animal models for autoimmune diseases.
  Tissue Antigens, 63, 383-394.  
15467726 M.A.Gronski, J.M.Boulter, D.Moskophidis, L.T.Nguyen, K.Holmberg, A.R.Elford, E.K.Deenick, H.O.Kim, J.M.Penninger, B.Odermatt, A.Gallimore, N.R.Gascoigne, and P.S.Ohashi (2004).
TCR affinity and negative regulation limit autoimmunity.
  Nat Med, 10, 1234-1239.  
  15100273 M.A.Mihalyo, A.D.Doody, J.P.McAleer, E.C.Nowak, M.Long, Y.Yang, and A.J.Adler (2004).
In vivo cyclophosphamide and IL-2 treatment impedes self-antigen-induced effector CD4 cell tolerization: implications for adoptive immunotherapy.
  J Immunol, 172, 5338-5345.  
14734527 M.Hülsmeyer, M.T.Fiorillo, F.Bettosini, R.Sorrentino, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2004).
Dual, HLA-B27 subtype-dependent conformation of a self-peptide.
  J Exp Med, 199, 271-281.
PDB codes: 1of2 1ogt
15306684 R.Hohlfeld, and H.Wekerle (2004).
Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines.
  Proc Natl Acad Sci U S A, 101, 14599-14606.  
15016009 S.Haahr, A.M.Plesner, B.F.Vestergaard, and P.Höllsberg (2004).
A role of late Epstein-Barr virus infection in multiple sclerosis.
  Acta Neurol Scand, 109, 270-275.  
15372502 T.P.Finn, R.E.Jones, C.Rich, R.Dahan, J.Link, C.S.David, Y.K.Chou, H.Offner, and A.A.Vandenbark (2004).
HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes.
  J Neurosci Res, 78, 100-114.  
14568977 A.Amedei, M.P.Bergman, B.J.Appelmelk, A.Azzurri, M.Benagiano, C.Tamburini, R.van der Zee, J.L.Telford, C.M.Vandenbroucke-Grauls, M.M.D'Elios, and G.Del Prete (2003).
Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity.
  J Exp Med, 198, 1147-1156.  
14977479 A.Fassas, and A.Kazis (2003).
High-dose immunosuppression and autologous hematopoietic stem cell rescue for severe multiple sclerosis.
  J Hematother Stem Cell Res, 12, 701-711.  
12648936 A.P.Kohm, K.G.Fuller, and S.D.Miller (2003).
Mimicking the way to autoimmunity: an evolving theory of sequence and structural homology.
  Trends Microbiol, 11, 101-105.  
12909456 D.Housset, and B.Malissen (2003).
What do TCR-pMHC crystal structures teach us about MHC restriction and alloreactivity?
  Trends Immunol, 24, 429-437.  
12665424 H.Wiendl, and B.C.Kieseier (2003).
Disease-modifying therapies in multiple sclerosis: an update on recent and ongoing trials and future strategies.
  Expert Opin Investig Drugs, 12, 689-712.  
12760396 I.A.Scarisbrick, and M.Rodriguez (2003).
Hit-Hit and hit-Run: viruses in the playing field of multiple sclerosis.
  Curr Neurol Neurosci Rep, 3, 265-271.  
14570827 M.Bradl, and R.Hohlfeld (2003).
Molecular pathogenesis of neuroinflammation.
  J Neurol Neurosurg Psychiatry, 74, 1364-1370.  
14609577 M.Long, A.D.Higgins, M.A.Mihalyo, and A.J.Adler (2003).
Effector CD4 cell tolerization is mediated through functional inactivation and involves preferential impairment of TNF-alpha and IFN-gamma expression potentials.
  Cell Immunol, 224, 114-121.  
14596882 M.P.Pender (2003).
Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune diseases.
  Trends Immunol, 24, 584-588.  
12628358 O.Neuhaus, J.J.Archelos, and H.P.Hartung (2003).
Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection.
  Trends Pharmacol Sci, 24, 131-138.  
12858060 T.Owens (2003).
The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage.
  Curr Opin Neurol, 16, 259-265.  
12952957 Z.Zavala-Ruiz, E.J.Sundberg, J.D.Stone, D.B.DeOliveira, I.C.Chan, J.Svendsen, R.A.Mariuzza, and L.J.Stern (2003).
Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1.
  J Biol Chem, 278, 44904-44912.
PDB code: 1pyw
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.