Crystal structures of T cell receptor β chains related to rheumatoid arthritis

Hongmin Li, Sandra Van Vranken, Yiwei Zhao, Zhong Li, Yi Guo, Leslie Eisele, Yixin Li

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The crystal structures of the Vβ17+ β chains of two human T cell receptors (TCRs), originally derived from the synovial fluid (SF4) and tissue (C5-1) of a patient with rheumatoid arthritis (RA), have been determined in native (SF4) and mutant (C5-1F104→Y/C187→S) forms, respectively. These TCR β chains form homodimers in solution and in crystals. Structural comparison reveals that the main-chain conformations in the CDR regions of the C5-1 and SF4 Vβ17 closely resemble those of a Vβ17 JM22 in a bound form; however, the CDR3 region shows different conformations among these three Vβ17 structures.At the side-chain level, conformational differences were observed at the CDR2 regions between our two ligand-free forms and the bound JM22 form. Other significant differences were observed at the Vβ regions 8-12, 40-44, and 82-88 between C5-1/SF4 and JM22 Vβ17, implying that there is considerable variability in the structures of very similar β chains. Structural alignments also reveal a considerable variation in the Vβ-Cβ associations, and this may affect ligand recognition. The crystal structures also provide insights into the structure basis of T cell recognition of Mycoplasma arthritidis mitogen (MAM), a superantigen that may be implicated in the development of human RA. Structural comparisons of the Vβ domains of known TCR structures indicate that there are significant similarities among Vβ regions that are MAM-reactive, whereas there appear to be significant structural differences among those Vβ regions that lack MAM-reactivity. It further reveals that CDR2 and framework region (FR) 3 are likely to account for the binding of TCR to MAM. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)3025-3038
Number of pages14
JournalProtein Science
Volume14
Issue number12
DOIs
StatePublished - Dec 2005
Externally publishedYes

Keywords

  • Crystal structure
  • Crystallography
  • Mutagenesis (site-directed and general)
  • Mycoplasma arthritidis mitogen
  • Protein crystallization
  • Protein structures - new
  • Proteins of the immune system
  • Rheumatoid arthritis
  • Structure/function studies
  • Superantigen
  • TCR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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