Alpha-amylase functions as a salivary gland-specific self T cell epitope in patients with Sjögren's syndrome.
Analyses of T cell receptors (TCR) on T cells infiltrating labial salivary glands of patients with Sjögren's syndrome (SS) indicate that the cells expand by antigen stimulation in context of major histocompatibility complex (MHC). To elucidate the autoantigens recognized by T cells infiltrating in labial salivary glands from patients with SS, proteins derived from human salivary gland cDNA libraries were screened by West-Western method using TCR-CDR3 probe, which is antigen recognition region of TCR on T cells. 13 cDNA clones were detected as proteins binding to TCR-CDR3 region. One was a human alpha-amylase salivary precursor (AA54-407), suggesting that alpha-amylase might be a salivary gland-specific autoantigen. To examine whether alpha-amylase acts as an antigen in labial salivary glands, PBL from 11 patients with SS were incubated with 9 different synthetic amino acids of alpha-amylase or salivary alpha-amylase. SSCP analysis on TCR clearly showed that alpha-amylase reactive T cells were observed in labial salivary glands from 3 of 11 patients with SS (27%). These findings support the possibility that alpha-amylase functions as a salivary gland-specific T cell epitope and induces autoimmunity in SS.
Matsumoto
I
I
Division of Rheumatology, Immunology, and Genetic Program, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Maeda
T
T
Takemoto
Y
Y
Hashimoto
Y
Y
Kimura
F
F
Iwamoto
I
I
Saito
Y
Y
Nishioka
K
K
Sumida
T
T
D000595:Amino Acid Sequence; D001324:Autoantigens; D015551:Autoimmunity; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000235:genetics; D004792:Enzyme Precursors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000939:Epitopes; D006801:Humans; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000201:enzymology* / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D000516:alpha-Amylases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D017931:DNA Primers; D004792:Enzyme Precursors; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell; D000516:alpha-Amylases