Modeling the Ternary Complex TCR-Vbeta/Collagenll (261-273)/ HLA-DR4 Associated with Rheumatoid Arthritis (Articolo in rivista)

Type
Label
  • Modeling the Ternary Complex TCR-Vbeta/Collagenll (261-273)/ HLA-DR4 Associated with Rheumatoid Arthritis (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • De Rosa Maria Cristina(1); Giardina Bruno(2); Bianchi Caterina(2); Carelli Alinovi Cristiana(2); Pirolli Davide(2); Ferraccioli Gianfranco(3); De Santis Maria(3); Di Sante Gabriele(4); Ria Francesco(4) (2010)
    Modeling the Ternary Complex TCR-Vbeta/Collagenll (261-273)/ HLA-DR4 Associated with Rheumatoid Arthritis
    in PloS one
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • De Rosa Maria Cristina(1); Giardina Bruno(2); Bianchi Caterina(2); Carelli Alinovi Cristiana(2); Pirolli Davide(2); Ferraccioli Gianfranco(3); De Santis Maria(3); Di Sante Gabriele(4); Ria Francesco(4) (literal)
Pagina inizio
  • e11550 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 5 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 11 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 7 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Rome, Italy; 2 Istituto di Biochimica e Biochimica Clinica, Universita` Cattolica del Sacro Cuore, Rome, Italy; 3 Dipartimento di Reumatologia, Universita` Cattolica del Sacro Cuore, Rome, Italy; 4 Istituto di Patologia Generale, Universita` Cattolica del Sacro Cuore, Rome, Italy (literal)
Titolo
  • Modeling the Ternary Complex TCR-Vbeta/Collagenll (261-273)/ HLA-DR4 Associated with Rheumatoid Arthritis (literal)
Abstract
  • Background: It is known that genetic predisposition to rheumatoid arthritis (RA) is associated with the MHC class II allele HLA-DR4 and that residues 261-273 of type II collagen (huCollp261) represent an immunodominant T cell epitope restricted by the DR4 molecule. Despite recent advances in characterization of MHC and T cell receptor (TCR) contacts to this epitope, the atomic details of TCR/huCollp261/HLA-DR4 ternary complex are not known. Methodology/Principal Findings: Here we have used computational modeling to get insight into this interaction. A three dimensional model of the TCR Vbeta domain from a DR4+ patient affected by RA has been derived by homology modeling techniques. Subsequently, the structure of the TCR Vbeta domain in complex with huCollp261/HLA-DR4 was obtained from a docking approach in conjunction with a filtering procedure based on biochemical information. The best complex from the docking experiments was then refined by 20 ns of molecular dynamics simulation in explicit water. The predicted model is consistent with available experimental data. Our results indicate that residues 97-101 of CDR3beta are critical for recognition of huCollp261/HLA-DR4 by TCR. We also show that TCR contacts on p/MHC surface affect the conformation of the shared epitope expressed by DR alleles associated with RA susceptibility. Conclusions/Significance: This work presents a three-dimensional model for the ternary complex TCR-Vbeta/collagenII(261-273)/HLA-DR4 associated with rheumatoid arthritis that can provide insights into the molecular mechanisms of self reactivity. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it