Conserved TCR β chain usage in reactive arthritis; evidence for selection by a putative HLA‐B27‐associated autoantigen
- 1 October 2002
- journal article
- research article
- Published by Wiley in Tissue Antigens
- Vol. 60 (4) , 299-308
- https://doi.org/10.1034/j.1399-0039.2002.600404.x
Abstract
Previous work suggested that expanded CD8+ T‐cell clones in the synovial fluid (SF) of HLA‐B27+ patients with reactive arthritis (ReA) preferentially use the T‐cell receptor variable region (TCRBV) 1, similar CDR3 sequences, and joining region (BJ) 2S3. To determine the range of conservation and disease‐specificity of CDR3‐sequences, we analyzed the TCRBV1‐J2S3 repertoire from 33 healthy HLA‐B27+ individuals, patients with various types of spondyloarthropathies (SpA), and with rheumatoid arthritis (RA) by CDR3‐spectratyping. After collection and database submission of all available TCRB‐CDR3 from HLA‐B27‐restricted or SpA‐derived T cells, we systematically screened the entire human sequence database for sequences similar to the B27/SpA‐related CDR3. Spectratyping revealed expanded T cell clones using conserved TCRBV1J2S3 in the SF from 5/6 of the patients with acute ReA but not among the controls. In database searches, 50 HLA‐B27 or SpA‐related CDR3‐sequences generated similar clusters of matched sequences, and matched reciprocally. Identical or closely related sequences were identified in 15 different individuals and a canonical ReA‐associated TCRB was defined [BV1‐CASSVG(V/I/L)(Y/F)STDTQYF‐J2S3]. All but one patient‐derived conserved sequences originated from acute stage ReA‐patients, and were not present among ∼3800 other human TCRB sequences in the database. Five of the conserved sequences originated from T cell clones that recognized uninfected cells in an HLA‐B27‐restricted fashion, implying a role of HLA‐B27‐restricted CD8+ T cells specific for a ubiquitous self‐ or cross‐reactive microbial determinant in the early phase of ReA. Related sequences were independently identified in four different laboratories. The consensus TCRB motif could be a helpful diagnostic marker in HLA‐B27‐associated ‘undifferentiated arthritis’.Keywords
This publication has 46 references indexed in Scilit:
- Glimpses at the recognition of peptide/MHC complexes by T‐cell antigen receptorsImmunological Reviews, 1998
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- Topology of T cell receptor-peptide/class I MHC interaction defined by charge reversal complementation and functional analysisJournal of Molecular Biology, 1997
- CD4+ Cell Oligoclonality in Crohn's Disease: Evidence for an Antigen-Specific ResponseHuman Immunology, 1996
- T-cell receptor usage in alloreactivity against HLA-B*2703 reveals significant conservation of the antigenic structure of B*2705Tissue Antigens, 1996
- Spread of clonal T-cell expansions in rheumatoid arthritis patientsHuman Immunology, 1996
- Clonal dominance and selection for similar complementarity determining region 3 motifs among T lymphocytes responding to the HLA-DR3-associated Mycobacterium leprae heat shock protein 65-KD peptide 3–13Human Immunology, 1995
- Identification of conserved T cell receptor CDR3 residues contacting known exposed peptide side chains from a major histocompatibility complex class I‐bound determinantEuropean Journal of Immunology, 1993
- Conservation of T cell receptor usage by HLA B27‐restricted influenza‐specific cytotoxic T lymphocytes suggests a general pattern for antigen‐specific major histocompatibility complex class I‐restricted responsesEuropean Journal of Immunology, 1993
- Peptide binding to empty HLA-B27 molecules of viable human cellsNature, 1991