Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren's syndrome.
Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS.
Matsumoto
I
I
Second Department of Internal Medicine, School of Medicine, Chiba Univesity, Japan.
Tsubota
K
K
Satake
Y
Y
Kita
Y
Y
Matsumura
R
R
Murata
H
H
Namekawa
T
T
Nishioka
K
K
Iwamoto
I
I
Saitoh
Y
Y
Sumida
T
T
D000595:Amino Acid Sequence; D001324:Autoantigens; D001483:Base Sequence; D001706:Biopsy; D015139:Blotting, Southern; D002999:Clone Cells; D006683:HLA-DQ Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007765:Lacrimal Apparatus / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012469:Salivary Glands / Q000276:immunology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes; D016693:Receptors, Antigen, T-Cell, alpha-beta