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Structural motifs in rheumatoid T-cell receptors
T Keiber-Emmons1, Q Fang, W Cai
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6100, USA.
DNA and Cell Biology
|March 21, 1998
Summary
Rheumatoid arthritis (RA) T-cell receptors (TCRs) show restricted diversity, suggesting a focused response to specific antigen-MHC complexes. Structural analysis reveals shared features in TCRs, supporting limited antigen recognition in RA pathogenesis.
Area of Science:
- Immunology
- Structural Biology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) pathogenesis involves T-cells, T-cell receptors (TCRs), and antigen (Ag) + major histocompatibility complex (MHC) interactions.
- Previous studies indicate restricted TCR transcript heterogeneity in RA, suggesting antigen-driven immune responses.
Purpose of the Study:
- To analyze sequence and structural features of RA-associated TCRs.
- To investigate potential shared antigen recognition mechanisms in RA.
Main Methods:
- Analysis of TCR sequences from synovial fluid, tissue, and peripheral blood.
- Molecular modeling of in vivo-activated synovial T-cell clones (Vbeta17/V alpha7).
- Comparison of TCR CDR3 structural and electrostatic properties.
Main Results:
- Preferential use of specific amino acid residues in TCR CDR3 regions, particularly alpha chains, in RA synovial samples.
- Identification of oligoclonal synovial TCR CDR3 groupings with similar lengths and compositions, implying shared antigen recognition.
- Molecular modeling revealed similar binding surfaces and central residue patches in distinct TCRs, suggesting an alpha-domain-focused recognition mechanism.
Conclusions:
- RA-associated TCRs recognize a limited diversity of antigen-MHC complexes.
- Structural similarities in TCRs support a focused antigen recognition model in RA pathogenesis.