Detection and epitope analysis of autoantigen-reactive T cells to the U1-small nuclear ribonucleoprotein A protein in autoimmune disease patients.
T cells that recognize autoantigens might play an important role in autoimmune diseases. To analyze "autoantigen-reactive T cell" in patients with an autoimmune disease, a human lymphocyte proliferation assay using soluble recombinant autoantigens has been conducted. PBMC from mixed connective tissue disease and SLE patients who possessed anti-U1-small nuclear ribonucleoprotein (snRNP) A autoantibodies responded to a recombinant U1-snRNP A protein. In contrast, PBMC from healthy subjects or autoimmune disease patients not possessing anti-U1-snRNP A autoantibodies did not show such responses. In addition, this proliferative response was inhibited by anti-CD4 mAb. Limiting dilution analyses revealed that the autoantigen-reactive T cells exist in relatively high frequency (1 of 4,065 to 1 of 23,256) in the mixed connective tissue disease patients. Moreover, by T cell epitope mapping, the T cell epitope area was found to be located in the C-terminus of the U1-snRNP A protein, overlapping the B cell epitope area that has been reported. These findings suggest the presence of autoantigen-reactive T cells in such patients, and when these T cells are activated, they may play a central role in the autoantibody generation.
Okubo
M
M
Division of Rheumatology and Molecular Immunology, St. Marianna University School of Medicine, Kawasaki-City, Japan.
Yamamoto
K
K
Kato
T
T
Matsuura
N
N
Nishimaki
T
T
Kasukawa
R
R
Ito
K
K
Mizushima
Y
Y
Nishioka
K
K
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002478:Cells, Cultured; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000939:Epitopes; D017412:Ribonucleoprotein, U1 Small Nuclear