Abstract
The U1-70kD autoantigen is a major target of B cell responses in patients with connective tissue diseases (CTD). T cell responses are important in the pathogenesis of CTD, however little is known about autoantigen-specific T cells in these diseases. We have recently proven that U1-70kD-reactive human T cells exist. To further characterize these autoreactive T cells, U1-70kD-reactive T cell clones have been generated from patients with CTD using either a recombinant fusion protein or synthetic peptides spanning the U1-70kD polypeptide. T cell receptors (TCR) isolated from the U1-70kD-reactive T cell clones were sequenced and the third complementarity-determining region (CDR3) compared to determine if a common motif was present. mAb blocking of antigen-induced proliferation was done to determine the HLA restriction element used in recognition of the U1-70kD autoantigen by T cells. The results presented here indicate that TCRAV CDR3 usage is highly restricted among U1-70kD autoantigen-specific human T cells clones derived from CTD patients with distinctive structural features. Furthermore, the recognition of the U1-70kD autoantigen occurs in the context of HLA-DR.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Autoantigens / immunology*
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Clone Cells
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Computer Simulation
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Connective Tissue Diseases / etiology
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Connective Tissue Diseases / immunology*
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Conserved Sequence
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Gene Rearrangement, T-Lymphocyte
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HLA-DR Antigens / immunology
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Humans
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Immunoglobulin Variable Region
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Lupus Erythematosus, Systemic / etiology
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Lupus Erythematosus, Systemic / immunology
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Mixed Connective Tissue Disease / etiology
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Mixed Connective Tissue Disease / immunology
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Models, Molecular
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Molecular Sequence Data
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Peptide Fragments / immunology
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Receptors, Antigen, T-Cell, alpha-beta*
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Ribonucleoprotein, U1 Small Nuclear / immunology*
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Sequence Analysis, DNA
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T-Lymphocytes / immunology*
Substances
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Autoantigens
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HLA-DR Antigens
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Immunoglobulin Variable Region
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Peptide Fragments
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Receptors, Antigen, T-Cell, alpha-beta
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Ribonucleoprotein, U1 Small Nuclear
Associated data
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GENBANK/AF009788
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GENBANK/AF009790
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GENBANK/AF009792
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GENBANK/AF086764
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GENBANK/AF086765
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GENBANK/AF086766
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GENBANK/AF086767
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GENBANK/AF086768
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GENBANK/AF086769
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GENBANK/AF086770
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GENBANK/AF087019
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GENBANK/U78307
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GENBANK/U83989
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GENBANK/U83990
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GENBANK/U84142
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GENBANK/U85050
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GENBANK/U85051
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GENBANK/U85052
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GENBANK/U85054
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GENBANK/U85394
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GENBANK/U85452