title: Divergence in the degree of clonal expansions in inflammatory T cell subpopulations mirrors HLA-associated risk alleles in genetically and clinically distinct subtypes of childhood arthritis.
abstract: Clinically distinct forms of childhood arthritis are associated with different risk alleles of polymorphic loci within the MHC, which code for the antigen-presenting class I or class II molecules. We have compared the TCR diversity of synovial T cells from children with enthesitis-related (HLA-B27(+)) arthritis and oligoarticular arthritis (with class II MHC risk allele associations) in parallel with peripheral blood T cells from each child, using a high-resolution heteroduplex TCR analysis. We demonstrate that multiple clonal T cell expansions are present and persistent within the joint in both groups, but that there is disease-specific divergence in the dominant T cell subset containing these expansions. Thus, the largest clonotypes within the inflamed joints of children with class II-associated arthritis are within the CD4(+) synovial T cell population, while the dominant clones from children with enthesitis-related arthritis (associated with a class I allele) are within the CD8(+) synovial T cell population. These data provide powerful data to support the concept that recognition of MHC-peptide complexes by T cells plays a role in the pathogenesis of juvenile arthritis.
authors.affiliation: Rheumatology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, UK. L.Wedderburn@ich.ucl.ac.uk
authors.forename: L R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: H
authors.initials: H
authors.lastname: Varsani
authors.forename: P
authors.initials: P
authors.lastname: Woo
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001171:Arthritis, Juvenile / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002648:Child; D002999:Clone Cells; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D012307:Risk Factors; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta