Clonotype analysis of peripheral blood T cells and autoantigen-reactive T cells from patients with mixed connective tissue disease.
T cells that recognize autoantigens may play a central role in the autoimmune response. We have previously shown that autoantigen-reactive T cells (CD4+) to U1-small nuclear ribonucleoprotein A were found in the PBMC of patients with systemic lupus erythematosus or mixed connective tissue disease. To reveal clonotypes of such T cells that spread to the periphery, T cell clonal accumulations and their TCR-beta chain variable gene usages in fresh PBMC from eight patients with mixed connective tissue disease were analyzed by a new method of single strand conformation polymorphism applying to TCR gene detection. The results revealed that the numbers of accumulated T cell clones (mean: 24.3 clones) were greater than the numbers of clones detected in healthy donors (mean: 4.0 clones). Frequently used V beta genes in these accumulated T cell clones were V beta 1, 3, 4, 5.2, 14, and 16. After the stimulation for these samples with the soluble recombinant U1-small nuclear ribonucleoprotein A protein, proliferative T cell responses were observed. We found that T cell clones expressing more restricted TCR V beta genes (1, 3, 5.2, and 14 families) accumulated in vitro. These results suggest that autoantigen-reactive oligoclonal T cell accumulations are present in the peripheral blood from systemic autoimmune disease patients.
Okubo
M
M
Second Department of Internal Medicine, Fukushima Medical College, Japan.
Kurokawa
M
M
Ohto
H
H
Nishimaki
T
T
Nishioka
K
K
Kasukawa
R
R
Yamamoto
K
K
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002999:Clone Cells; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D008213:Lymphocyte Activation; D008947:Mixed Connective Tissue Disease / Q000276:immunology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics*; D012261:Ribonucleoproteins / Q000276:immunology*; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012261:Ribonucleoproteins