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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. CONCLUSION: 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.

Original publication

DOI

10.1002/1529-0131(200201)46:1<209::aid-art10066>3.0.co;2-1

Type

Journal article

Journal

Arthritis and rheumatism

Publication Date

01/2002

Volume

46

Pages

209 - 214

Addresses

The Medical School, University of Birmingham, UK

Keywords

T-Lymphocytes, Humans, Sjogren's Syndrome, Lupus Erythematosus, Systemic, Caspases, Peptide Fragments, Ribonucleoproteins, Antibodies, Antinuclear, HLA-DQ Antigens, HLA-DR1 Antigen, HLA-DR4 Antigen, Autoantigens, Epitope Mapping, Cell Division, Amino Acid Sequence, Molecular Sequence Data