Candidate T cell epitopes of the human La/SSB autoantigen.
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.
Davies
Marie L
ML
The Medical School, University of Birmingham, UK
Taylor
Emma J
EJ
Gordon
Caroline
C
Young
Stephen P
SP
Welsh
Ken
K
Bunce
Mike
M
Wordsworth
B Paul
BP
Davidson
Brian
B
Bowman
Simon J
SJ
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
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