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Ge C, Weisse S, Xu B, et al. Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor. Ann Rheum Dis. 2022;doi: 10.1136/annrheumdis-2021-220500.
Ge, C., Weisse, S., Xu, B., Dobritzsch, D., Viljanen, J., Kihlberg, J., Do, N. N., Schneider, N., Lanig, H., Holmdahl, R., & Burkhardt, H. (2022). Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor. Annals of the rheumatic diseases, . https://doi.org/10.1136/annrheumdis-2021-220500
Ge, Changrong, et al. "Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor." Annals of the rheumatic diseases vol. (2022). doi: https://doi.org/10.1136/annrheumdis-2021-220500
Ge C, Weisse S, Xu B, Dobritzsch D, Viljanen J, Kihlberg J, Do NN, Schneider N, Lanig H, Holmdahl R, Burkhardt H. Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor. Ann Rheum Dis. 2022 Jan 13; doi: 10.1136/annrheumdis-2021-220500. Epub 2022 Jan 13. PMID: 35027402.
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Ann Rheum Dis. 2022 Jan 13; doi: 10.1136/annrheumdis-2021-220500. Epub 2022 Jan 13.

Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor.

Annals of the rheumatic diseases

Changrong Ge, Sylvia Weisse, Bingze Xu, Doreen Dobritzsch, Johan Viljanen, Jan Kihlberg, Nhu-Nguyen Do, Nadine Schneider, Harald Lanig, Rikard Holmdahl, Harald Burkhardt

Affiliations

  1. Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  2. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
  3. Section of Biochemistry, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
  4. Section of Organic Chemistry, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
  5. Central Institute for Scientific Computing (ZISC), Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  6. Erlangen National High Performance Computing Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany (current affiliation).
  7. Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
  8. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany [email protected].
  9. Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Frankfurt am Main, Germany.
  10. Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.

PMID: 35027402 DOI: 10.1136/annrheumdis-2021-220500

Abstract

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease strongly associated with the major histocompatibility complex (MHC) class II allele DRB1*04:01, which encodes a protein that binds self-peptides for presentation to T cells. This study characterises the autoantigen-presenting function of DRB1*04:01 (HLA-DRA*01:01/HLA-DRB1*04:01) at a molecular level for prototypic T-cell determinants, focusing on a post-translationally modified collagen type II (Col2)-derived peptide.

METHODS: The crystal structures of DRB1*04:01 molecules in complex with the peptides HSP70

RESULTS: The crystal structures identified peptide binding to DRB1*04:01 and potential side chain exposure to T cells. The main TCR recognition sites in Col2

CONCLUSIONS: The MHC-peptide-TCR interactions elucidated in our study provide new molecular insights into recognition of a post-translationally modified RA T-cell determinant with a known dominant role in arthritogenic and tolerogenic responses in murine Col2-induced arthritis.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords: T-lymphocyte subsets; autoimmunity; rheumatoid arthritis

Conflict of interest statement

Competing interests: NS, BX, SW, RH and HB are listed as inventors on Patent EP2020072287 (https://www.onscope.com/ipowner/en/ip/ptwo/EP2020072287.html). SW, N-ND, RH and HB are lasted as inventors on

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