title: Candidate T cell epitopes of the human La/SSB autoantigen.
abstract: OBJECTIVE
  To identify T cell epitopes of the human La autoantigen involved in the generation of anti-Ro/La autoantibodies.
  
  
  METHODS
  Molecular techniques were used for HLA typing of 219 white patients with systemic lupus erythematosus and 125 white patients with primary Sjögren's syndrome. Anti-Ro/La antibody levels were measured by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cell responses to an overlapping series of synthetic 15-mer peptides spanning the entire La sequence were examined in pools or individually in conventional 7-day proliferation assays.
  
  
  RESULTS
  HLA typing confirmed that the HLA-DR3/DQ2 haplotype is closely associated with the occurrence of anti-Ro/La antibodies, and that the frequency of HLA-DR1 and DR4 haplotypes is reduced among antibody-positive patients. We identified 3 regions of the La sequence likely to contain T cell epitopes and 1 peptide, La 49-63, that generated a low-level but clear-cut T cell proliferative response. The HLA restrictions of these responses mirrored the HLA association data from the cohort study. Among individuals who were HLA-DR3 positive, there was no difference between patients and controls in the proliferative response to the La 49-63 peptide.
  
  
  CONCLUSIONS
  Our data suggest that these are naive T cell responses, and that the identification of T cell epitopes involved in the generation of anti-Ro/La autoantibodies should focus on alternative candidate antigens.
authors.affiliation: The Medical School, University of Birmingham, UK
authors.forename: Marie L
authors.initials: ML
authors.lastname: Davies
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Taylor
authors.forename: Caroline
authors.initials: C
authors.lastname: Gordon
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Young
authors.forename: Ken
authors.initials: K
authors.lastname: Welsh
authors.forename: Mike
authors.initials: M
authors.lastname: Bunce
authors.forename: B Paul
authors.initials: BP
authors.lastname: Wordsworth
authors.forename: Brian
authors.initials: B
authors.lastname: Davidson
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Bowman
mesh_terms: D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D018604:Epitope Mapping; D006683:HLA-DQ Antigens / Q000032:analysis; D015798:HLA-DR1 Antigen / Q000032:analysis; D015804:HLA-DR4 Antigen / Q000032:analysis; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D000097585:SS-B Antigen
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D020169:Caspases; D006683:HLA-DQ Antigens; D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D010446:Peptide Fragments; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C053186:HLA-DQ2 antigen; C035356:SS-A antibodies